An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma
Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD+). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we r...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Gujar, Amit D [verfasserIn] |
|---|
| Format: |
Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2016 |
|---|
| Schlagwörter: |
|---|
| Übergeordnetes Werk: |
Enthalten in: Proceedings of the National Academy of Sciences of the United States of America - Washington, DC : NAS, 1877, 113(2016), 51, Seite E8247-E8256 |
|---|---|
| Übergeordnetes Werk: |
volume:113 ; year:2016 ; number:51 ; pages:E8247-E8256 |
| Links: |
|---|
| DOI / URN: |
10.1073/pnas.1610921114 |
|---|
| Katalog-ID: |
OLC1989958419 |
|---|
| LEADER | 01000caa a2200265 4500 | ||
|---|---|---|---|
| 001 | OLC1989958419 | ||
| 003 | DE-627 | ||
| 005 | 20230715030740.0 | ||
| 007 | tu | ||
| 008 | 170207s2016 xx ||||| 00| ||eng c | ||
| 024 | 7 | |a 10.1073/pnas.1610921114 |2 doi | |
| 028 | 5 | 2 | |a PQ20170206 |
| 035 | |a (DE-627)OLC1989958419 | ||
| 035 | |a (DE-599)GBVOLC1989958419 | ||
| 035 | |a (PRQ)c1045-f39e84d25739e8c65faa0ab6a67bad476081f838f307215d3b23bb451e8c266e0 | ||
| 035 | |a (KEY)0583363920160000113005108247naddependenttranscriptionalprogramgovernsselfrenew | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 500 |q DNB |
| 082 | 0 | 4 | |a 570 |q AVZ |
| 084 | |a LING |2 fid | ||
| 084 | |a BIODIV |2 fid | ||
| 100 | 1 | |a Gujar, Amit D |e verfasserin |4 aut | |
| 245 | 1 | 3 | |a An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma |
| 264 | 1 | |c 2016 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 520 | |a Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD+). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD+ synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival. Pharmacological and genetic inhibition of NAMPT decreased NAD+ levels and GSC self-renewal capacity, and NAMPT knockdown inhibited the in vivo tumorigenicity of GSCs. Regulatory network analysis of RNA sequencing data using GSCs treated with NAMPT inhibitor identified transcription factor E2F2 as the center of a transcriptional hub in the NAD+-dependent network. Accordingly, we demonstrate E2F2 is required for GSC self-renewal. Downstream, E2F2 drives the transcription of members of the inhibitor of differentiation (ID) helix-loop-helix gene family. Finally, we find NAMPT mediates GSC radiation resistance. The identification of a NAMPT-E2F2-ID axis establishes a link between NAD+ metabolism and a self-renewal transcriptional program in glioblastoma, with therapeutic implications for this formidable cancer. | ||
| 650 | 4 | |a Ribonucleic acid--RNA | |
| 650 | 4 | |a Stem cells | |
| 650 | 4 | |a Correlation analysis | |
| 650 | 4 | |a Tumors | |
| 650 | 4 | |a Cancer | |
| 650 | 4 | |a Signal transduction | |
| 700 | 1 | |a Le, Son |4 oth | |
| 700 | 1 | |a Mao, Diane D |4 oth | |
| 700 | 1 | |a Dadey, David Y. A |4 oth | |
| 700 | 1 | |a Turski, Alice |4 oth | |
| 700 | 1 | |a Sasaki, Yo |4 oth | |
| 700 | 1 | |a Aum, Diane |4 oth | |
| 700 | 1 | |a Luo, Jingqin |4 oth | |
| 700 | 1 | |a Dahiya, Sonika |4 oth | |
| 700 | 1 | |a Yuan, Liya |4 oth | |
| 700 | 1 | |a Rich, Keith M |4 oth | |
| 700 | 1 | |a Milbrandt, Jeffrey |4 oth | |
| 700 | 1 | |a Hallahan, Dennis E |4 oth | |
| 700 | 1 | |a Yano, Hiroko |4 oth | |
| 700 | 1 | |a Tran, David D |4 oth | |
| 700 | 1 | |a Kim, Albert H |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Proceedings of the National Academy of Sciences of the United States of America |d Washington, DC : NAS, 1877 |g 113(2016), 51, Seite E8247-E8256 |w (DE-627)129505269 |w (DE-600)209104-5 |w (DE-576)014909189 |x 0027-8424 |7 nnns |
| 773 | 1 | 8 | |g volume:113 |g year:2016 |g number:51 |g pages:E8247-E8256 |
| 856 | 4 | 1 | |u http://dx.doi.org/10.1073/pnas.1610921114 |3 Volltext |
| 856 | 4 | 2 | |u http://search.proquest.com/docview/1853314761 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_OLC | ||
| 912 | |a FID-LING | ||
| 912 | |a FID-BIODIV | ||
| 912 | |a SSG-OLC-PHY | ||
| 912 | |a SSG-OLC-CHE | ||
| 912 | |a SSG-OLC-MAT | ||
| 912 | |a SSG-OLC-FOR | ||
| 912 | |a SSG-OLC-PHA | ||
| 912 | |a SSG-OLC-DE-84 | ||
| 912 | |a SSG-OPC-MAT | ||
| 912 | |a SSG-OPC-FOR | ||
| 912 | |a GBV_ILN_40 | ||
| 912 | |a GBV_ILN_59 | ||
| 951 | |a AR | ||
| 952 | |d 113 |j 2016 |e 51 |h E8247-E8256 | ||
| author_variant |
a d g ad adg |
|---|---|
| matchkey_str |
article:00278424:2016----::nadpnetrncitoapormoenslrnwlnrdain |
| hierarchy_sort_str |
2016 |
| publishDate |
2016 |
| allfields |
10.1073/pnas.1610921114 doi PQ20170206 (DE-627)OLC1989958419 (DE-599)GBVOLC1989958419 (PRQ)c1045-f39e84d25739e8c65faa0ab6a67bad476081f838f307215d3b23bb451e8c266e0 (KEY)0583363920160000113005108247naddependenttranscriptionalprogramgovernsselfrenew DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Gujar, Amit D verfasserin aut An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD+). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD+ synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival. Pharmacological and genetic inhibition of NAMPT decreased NAD+ levels and GSC self-renewal capacity, and NAMPT knockdown inhibited the in vivo tumorigenicity of GSCs. Regulatory network analysis of RNA sequencing data using GSCs treated with NAMPT inhibitor identified transcription factor E2F2 as the center of a transcriptional hub in the NAD+-dependent network. Accordingly, we demonstrate E2F2 is required for GSC self-renewal. Downstream, E2F2 drives the transcription of members of the inhibitor of differentiation (ID) helix-loop-helix gene family. Finally, we find NAMPT mediates GSC radiation resistance. The identification of a NAMPT-E2F2-ID axis establishes a link between NAD+ metabolism and a self-renewal transcriptional program in glioblastoma, with therapeutic implications for this formidable cancer. Ribonucleic acid--RNA Stem cells Correlation analysis Tumors Cancer Signal transduction Le, Son oth Mao, Diane D oth Dadey, David Y. A oth Turski, Alice oth Sasaki, Yo oth Aum, Diane oth Luo, Jingqin oth Dahiya, Sonika oth Yuan, Liya oth Rich, Keith M oth Milbrandt, Jeffrey oth Hallahan, Dennis E oth Yano, Hiroko oth Tran, David D oth Kim, Albert H oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 113(2016), 51, Seite E8247-E8256 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:113 year:2016 number:51 pages:E8247-E8256 http://dx.doi.org/10.1073/pnas.1610921114 Volltext http://search.proquest.com/docview/1853314761 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 113 2016 51 E8247-E8256 |
| spelling |
10.1073/pnas.1610921114 doi PQ20170206 (DE-627)OLC1989958419 (DE-599)GBVOLC1989958419 (PRQ)c1045-f39e84d25739e8c65faa0ab6a67bad476081f838f307215d3b23bb451e8c266e0 (KEY)0583363920160000113005108247naddependenttranscriptionalprogramgovernsselfrenew DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Gujar, Amit D verfasserin aut An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD+). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD+ synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival. Pharmacological and genetic inhibition of NAMPT decreased NAD+ levels and GSC self-renewal capacity, and NAMPT knockdown inhibited the in vivo tumorigenicity of GSCs. Regulatory network analysis of RNA sequencing data using GSCs treated with NAMPT inhibitor identified transcription factor E2F2 as the center of a transcriptional hub in the NAD+-dependent network. Accordingly, we demonstrate E2F2 is required for GSC self-renewal. Downstream, E2F2 drives the transcription of members of the inhibitor of differentiation (ID) helix-loop-helix gene family. Finally, we find NAMPT mediates GSC radiation resistance. The identification of a NAMPT-E2F2-ID axis establishes a link between NAD+ metabolism and a self-renewal transcriptional program in glioblastoma, with therapeutic implications for this formidable cancer. Ribonucleic acid--RNA Stem cells Correlation analysis Tumors Cancer Signal transduction Le, Son oth Mao, Diane D oth Dadey, David Y. A oth Turski, Alice oth Sasaki, Yo oth Aum, Diane oth Luo, Jingqin oth Dahiya, Sonika oth Yuan, Liya oth Rich, Keith M oth Milbrandt, Jeffrey oth Hallahan, Dennis E oth Yano, Hiroko oth Tran, David D oth Kim, Albert H oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 113(2016), 51, Seite E8247-E8256 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:113 year:2016 number:51 pages:E8247-E8256 http://dx.doi.org/10.1073/pnas.1610921114 Volltext http://search.proquest.com/docview/1853314761 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 113 2016 51 E8247-E8256 |
| allfields_unstemmed |
10.1073/pnas.1610921114 doi PQ20170206 (DE-627)OLC1989958419 (DE-599)GBVOLC1989958419 (PRQ)c1045-f39e84d25739e8c65faa0ab6a67bad476081f838f307215d3b23bb451e8c266e0 (KEY)0583363920160000113005108247naddependenttranscriptionalprogramgovernsselfrenew DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Gujar, Amit D verfasserin aut An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD+). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD+ synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival. Pharmacological and genetic inhibition of NAMPT decreased NAD+ levels and GSC self-renewal capacity, and NAMPT knockdown inhibited the in vivo tumorigenicity of GSCs. Regulatory network analysis of RNA sequencing data using GSCs treated with NAMPT inhibitor identified transcription factor E2F2 as the center of a transcriptional hub in the NAD+-dependent network. Accordingly, we demonstrate E2F2 is required for GSC self-renewal. Downstream, E2F2 drives the transcription of members of the inhibitor of differentiation (ID) helix-loop-helix gene family. Finally, we find NAMPT mediates GSC radiation resistance. The identification of a NAMPT-E2F2-ID axis establishes a link between NAD+ metabolism and a self-renewal transcriptional program in glioblastoma, with therapeutic implications for this formidable cancer. Ribonucleic acid--RNA Stem cells Correlation analysis Tumors Cancer Signal transduction Le, Son oth Mao, Diane D oth Dadey, David Y. A oth Turski, Alice oth Sasaki, Yo oth Aum, Diane oth Luo, Jingqin oth Dahiya, Sonika oth Yuan, Liya oth Rich, Keith M oth Milbrandt, Jeffrey oth Hallahan, Dennis E oth Yano, Hiroko oth Tran, David D oth Kim, Albert H oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 113(2016), 51, Seite E8247-E8256 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:113 year:2016 number:51 pages:E8247-E8256 http://dx.doi.org/10.1073/pnas.1610921114 Volltext http://search.proquest.com/docview/1853314761 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 113 2016 51 E8247-E8256 |
| allfieldsGer |
10.1073/pnas.1610921114 doi PQ20170206 (DE-627)OLC1989958419 (DE-599)GBVOLC1989958419 (PRQ)c1045-f39e84d25739e8c65faa0ab6a67bad476081f838f307215d3b23bb451e8c266e0 (KEY)0583363920160000113005108247naddependenttranscriptionalprogramgovernsselfrenew DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Gujar, Amit D verfasserin aut An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD+). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD+ synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival. Pharmacological and genetic inhibition of NAMPT decreased NAD+ levels and GSC self-renewal capacity, and NAMPT knockdown inhibited the in vivo tumorigenicity of GSCs. Regulatory network analysis of RNA sequencing data using GSCs treated with NAMPT inhibitor identified transcription factor E2F2 as the center of a transcriptional hub in the NAD+-dependent network. Accordingly, we demonstrate E2F2 is required for GSC self-renewal. Downstream, E2F2 drives the transcription of members of the inhibitor of differentiation (ID) helix-loop-helix gene family. Finally, we find NAMPT mediates GSC radiation resistance. The identification of a NAMPT-E2F2-ID axis establishes a link between NAD+ metabolism and a self-renewal transcriptional program in glioblastoma, with therapeutic implications for this formidable cancer. Ribonucleic acid--RNA Stem cells Correlation analysis Tumors Cancer Signal transduction Le, Son oth Mao, Diane D oth Dadey, David Y. A oth Turski, Alice oth Sasaki, Yo oth Aum, Diane oth Luo, Jingqin oth Dahiya, Sonika oth Yuan, Liya oth Rich, Keith M oth Milbrandt, Jeffrey oth Hallahan, Dennis E oth Yano, Hiroko oth Tran, David D oth Kim, Albert H oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 113(2016), 51, Seite E8247-E8256 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:113 year:2016 number:51 pages:E8247-E8256 http://dx.doi.org/10.1073/pnas.1610921114 Volltext http://search.proquest.com/docview/1853314761 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 113 2016 51 E8247-E8256 |
| allfieldsSound |
10.1073/pnas.1610921114 doi PQ20170206 (DE-627)OLC1989958419 (DE-599)GBVOLC1989958419 (PRQ)c1045-f39e84d25739e8c65faa0ab6a67bad476081f838f307215d3b23bb451e8c266e0 (KEY)0583363920160000113005108247naddependenttranscriptionalprogramgovernsselfrenew DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Gujar, Amit D verfasserin aut An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD+). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD+ synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival. Pharmacological and genetic inhibition of NAMPT decreased NAD+ levels and GSC self-renewal capacity, and NAMPT knockdown inhibited the in vivo tumorigenicity of GSCs. Regulatory network analysis of RNA sequencing data using GSCs treated with NAMPT inhibitor identified transcription factor E2F2 as the center of a transcriptional hub in the NAD+-dependent network. Accordingly, we demonstrate E2F2 is required for GSC self-renewal. Downstream, E2F2 drives the transcription of members of the inhibitor of differentiation (ID) helix-loop-helix gene family. Finally, we find NAMPT mediates GSC radiation resistance. The identification of a NAMPT-E2F2-ID axis establishes a link between NAD+ metabolism and a self-renewal transcriptional program in glioblastoma, with therapeutic implications for this formidable cancer. Ribonucleic acid--RNA Stem cells Correlation analysis Tumors Cancer Signal transduction Le, Son oth Mao, Diane D oth Dadey, David Y. A oth Turski, Alice oth Sasaki, Yo oth Aum, Diane oth Luo, Jingqin oth Dahiya, Sonika oth Yuan, Liya oth Rich, Keith M oth Milbrandt, Jeffrey oth Hallahan, Dennis E oth Yano, Hiroko oth Tran, David D oth Kim, Albert H oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 113(2016), 51, Seite E8247-E8256 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:113 year:2016 number:51 pages:E8247-E8256 http://dx.doi.org/10.1073/pnas.1610921114 Volltext http://search.proquest.com/docview/1853314761 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 113 2016 51 E8247-E8256 |
| language |
English |
| source |
Enthalten in Proceedings of the National Academy of Sciences of the United States of America 113(2016), 51, Seite E8247-E8256 volume:113 year:2016 number:51 pages:E8247-E8256 |
| sourceStr |
Enthalten in Proceedings of the National Academy of Sciences of the United States of America 113(2016), 51, Seite E8247-E8256 volume:113 year:2016 number:51 pages:E8247-E8256 |
| format_phy_str_mv |
Article |
| institution |
findex.gbv.de |
| topic_facet |
Ribonucleic acid--RNA Stem cells Correlation analysis Tumors Cancer Signal transduction |
| dewey-raw |
500 |
| isfreeaccess_bool |
false |
| container_title |
Proceedings of the National Academy of Sciences of the United States of America |
| authorswithroles_txt_mv |
Gujar, Amit D @@aut@@ Le, Son @@oth@@ Mao, Diane D @@oth@@ Dadey, David Y. A @@oth@@ Turski, Alice @@oth@@ Sasaki, Yo @@oth@@ Aum, Diane @@oth@@ Luo, Jingqin @@oth@@ Dahiya, Sonika @@oth@@ Yuan, Liya @@oth@@ Rich, Keith M @@oth@@ Milbrandt, Jeffrey @@oth@@ Hallahan, Dennis E @@oth@@ Yano, Hiroko @@oth@@ Tran, David D @@oth@@ Kim, Albert H @@oth@@ |
| publishDateDaySort_date |
2016-01-01T00:00:00Z |
| hierarchy_top_id |
129505269 |
| dewey-sort |
3500 |
| id |
OLC1989958419 |
| language_de |
englisch |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a2200265 4500</leader><controlfield tag="001">OLC1989958419</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230715030740.0</controlfield><controlfield tag="007">tu</controlfield><controlfield tag="008">170207s2016 xx ||||| 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1073/pnas.1610921114</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">PQ20170206</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)OLC1989958419</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)GBVOLC1989958419</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(PRQ)c1045-f39e84d25739e8c65faa0ab6a67bad476081f838f307215d3b23bb451e8c266e0</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(KEY)0583363920160000113005108247naddependenttranscriptionalprogramgovernsselfrenew</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">500</subfield><subfield code="q">DNB</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">570</subfield><subfield code="q">AVZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">LING</subfield><subfield code="2">fid</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">BIODIV</subfield><subfield code="2">fid</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Gujar, Amit D</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="3"><subfield code="a">An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2016</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">ohne Hilfsmittel zu benutzen</subfield><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Band</subfield><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD+). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD+ synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival. Pharmacological and genetic inhibition of NAMPT decreased NAD+ levels and GSC self-renewal capacity, and NAMPT knockdown inhibited the in vivo tumorigenicity of GSCs. Regulatory network analysis of RNA sequencing data using GSCs treated with NAMPT inhibitor identified transcription factor E2F2 as the center of a transcriptional hub in the NAD+-dependent network. Accordingly, we demonstrate E2F2 is required for GSC self-renewal. Downstream, E2F2 drives the transcription of members of the inhibitor of differentiation (ID) helix-loop-helix gene family. Finally, we find NAMPT mediates GSC radiation resistance. The identification of a NAMPT-E2F2-ID axis establishes a link between NAD+ metabolism and a self-renewal transcriptional program in glioblastoma, with therapeutic implications for this formidable cancer.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Ribonucleic acid--RNA</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Stem cells</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Correlation analysis</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tumors</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Cancer</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Signal transduction</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Le, Son</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Mao, Diane D</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Dadey, David Y. A</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Turski, Alice</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sasaki, Yo</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Aum, Diane</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Luo, Jingqin</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Dahiya, Sonika</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Yuan, Liya</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Rich, Keith M</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Milbrandt, Jeffrey</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hallahan, Dennis E</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Yano, Hiroko</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tran, David D</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kim, Albert H</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Proceedings of the National Academy of Sciences of the United States of America</subfield><subfield code="d">Washington, DC : NAS, 1877</subfield><subfield code="g">113(2016), 51, Seite E8247-E8256</subfield><subfield code="w">(DE-627)129505269</subfield><subfield code="w">(DE-600)209104-5</subfield><subfield code="w">(DE-576)014909189</subfield><subfield code="x">0027-8424</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:113</subfield><subfield code="g">year:2016</subfield><subfield code="g">number:51</subfield><subfield code="g">pages:E8247-E8256</subfield></datafield><datafield tag="856" ind1="4" ind2="1"><subfield code="u">http://dx.doi.org/10.1073/pnas.1610921114</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://search.proquest.com/docview/1853314761</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_OLC</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">FID-LING</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">FID-BIODIV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHY</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-CHE</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-MAT</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-DE-84</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-MAT</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_59</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">113</subfield><subfield code="j">2016</subfield><subfield code="e">51</subfield><subfield code="h">E8247-E8256</subfield></datafield></record></collection>
|
| author |
Gujar, Amit D |
| spellingShingle |
Gujar, Amit D ddc 500 ddc 570 fid LING fid BIODIV misc Ribonucleic acid--RNA misc Stem cells misc Correlation analysis misc Tumors misc Cancer misc Signal transduction An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma |
| authorStr |
Gujar, Amit D |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)129505269 |
| format |
Article |
| dewey-ones |
500 - Natural sciences & mathematics 570 - Life sciences; biology |
| delete_txt_mv |
keep |
| author_role |
aut |
| collection |
OLC |
| remote_str |
false |
| illustrated |
Not Illustrated |
| issn |
0027-8424 |
| topic_title |
500 DNB 570 AVZ LING fid BIODIV fid An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma Ribonucleic acid--RNA Stem cells Correlation analysis Tumors Cancer Signal transduction |
| topic |
ddc 500 ddc 570 fid LING fid BIODIV misc Ribonucleic acid--RNA misc Stem cells misc Correlation analysis misc Tumors misc Cancer misc Signal transduction |
| topic_unstemmed |
ddc 500 ddc 570 fid LING fid BIODIV misc Ribonucleic acid--RNA misc Stem cells misc Correlation analysis misc Tumors misc Cancer misc Signal transduction |
| topic_browse |
ddc 500 ddc 570 fid LING fid BIODIV misc Ribonucleic acid--RNA misc Stem cells misc Correlation analysis misc Tumors misc Cancer misc Signal transduction |
| format_facet |
Aufsätze Gedruckte Aufsätze |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
nc |
| author2_variant |
s l sl d d m dd ddm d y a d dya dyad a t at y s ys d a da j l jl s d sd l y ly k m r km kmr j m jm d e h de deh h y hy d d t dd ddt a h k ah ahk |
| hierarchy_parent_title |
Proceedings of the National Academy of Sciences of the United States of America |
| hierarchy_parent_id |
129505269 |
| dewey-tens |
500 - Science 570 - Life sciences; biology |
| hierarchy_top_title |
Proceedings of the National Academy of Sciences of the United States of America |
| isfreeaccess_txt |
false |
| familylinks_str_mv |
(DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 |
| title |
An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma |
| ctrlnum |
(DE-627)OLC1989958419 (DE-599)GBVOLC1989958419 (PRQ)c1045-f39e84d25739e8c65faa0ab6a67bad476081f838f307215d3b23bb451e8c266e0 (KEY)0583363920160000113005108247naddependenttranscriptionalprogramgovernsselfrenew |
| title_full |
An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma |
| author_sort |
Gujar, Amit D |
| journal |
Proceedings of the National Academy of Sciences of the United States of America |
| journalStr |
Proceedings of the National Academy of Sciences of the United States of America |
| lang_code |
eng |
| isOA_bool |
false |
| dewey-hundreds |
500 - Science |
| recordtype |
marc |
| publishDateSort |
2016 |
| contenttype_str_mv |
txt |
| author_browse |
Gujar, Amit D |
| container_volume |
113 |
| class |
500 DNB 570 AVZ LING fid BIODIV fid |
| format_se |
Aufsätze |
| author-letter |
Gujar, Amit D |
| doi_str_mv |
10.1073/pnas.1610921114 |
| dewey-full |
500 570 |
| title_sort |
nad+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma |
| title_auth |
An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma |
| abstract |
Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD+). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD+ synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival. Pharmacological and genetic inhibition of NAMPT decreased NAD+ levels and GSC self-renewal capacity, and NAMPT knockdown inhibited the in vivo tumorigenicity of GSCs. Regulatory network analysis of RNA sequencing data using GSCs treated with NAMPT inhibitor identified transcription factor E2F2 as the center of a transcriptional hub in the NAD+-dependent network. Accordingly, we demonstrate E2F2 is required for GSC self-renewal. Downstream, E2F2 drives the transcription of members of the inhibitor of differentiation (ID) helix-loop-helix gene family. Finally, we find NAMPT mediates GSC radiation resistance. The identification of a NAMPT-E2F2-ID axis establishes a link between NAD+ metabolism and a self-renewal transcriptional program in glioblastoma, with therapeutic implications for this formidable cancer. |
| abstractGer |
Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD+). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD+ synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival. Pharmacological and genetic inhibition of NAMPT decreased NAD+ levels and GSC self-renewal capacity, and NAMPT knockdown inhibited the in vivo tumorigenicity of GSCs. Regulatory network analysis of RNA sequencing data using GSCs treated with NAMPT inhibitor identified transcription factor E2F2 as the center of a transcriptional hub in the NAD+-dependent network. Accordingly, we demonstrate E2F2 is required for GSC self-renewal. Downstream, E2F2 drives the transcription of members of the inhibitor of differentiation (ID) helix-loop-helix gene family. Finally, we find NAMPT mediates GSC radiation resistance. The identification of a NAMPT-E2F2-ID axis establishes a link between NAD+ metabolism and a self-renewal transcriptional program in glioblastoma, with therapeutic implications for this formidable cancer. |
| abstract_unstemmed |
Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD+). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD+ synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival. Pharmacological and genetic inhibition of NAMPT decreased NAD+ levels and GSC self-renewal capacity, and NAMPT knockdown inhibited the in vivo tumorigenicity of GSCs. Regulatory network analysis of RNA sequencing data using GSCs treated with NAMPT inhibitor identified transcription factor E2F2 as the center of a transcriptional hub in the NAD+-dependent network. Accordingly, we demonstrate E2F2 is required for GSC self-renewal. Downstream, E2F2 drives the transcription of members of the inhibitor of differentiation (ID) helix-loop-helix gene family. Finally, we find NAMPT mediates GSC radiation resistance. The identification of a NAMPT-E2F2-ID axis establishes a link between NAD+ metabolism and a self-renewal transcriptional program in glioblastoma, with therapeutic implications for this formidable cancer. |
| collection_details |
GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 |
| container_issue |
51 |
| title_short |
An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma |
| url |
http://dx.doi.org/10.1073/pnas.1610921114 http://search.proquest.com/docview/1853314761 |
| remote_bool |
false |
| author2 |
Le, Son Mao, Diane D Dadey, David Y. A Turski, Alice Sasaki, Yo Aum, Diane Luo, Jingqin Dahiya, Sonika Yuan, Liya Rich, Keith M Milbrandt, Jeffrey Hallahan, Dennis E Yano, Hiroko Tran, David D Kim, Albert H |
| author2Str |
Le, Son Mao, Diane D Dadey, David Y. A Turski, Alice Sasaki, Yo Aum, Diane Luo, Jingqin Dahiya, Sonika Yuan, Liya Rich, Keith M Milbrandt, Jeffrey Hallahan, Dennis E Yano, Hiroko Tran, David D Kim, Albert H |
| ppnlink |
129505269 |
| mediatype_str_mv |
n |
| isOA_txt |
false |
| hochschulschrift_bool |
false |
| author2_role |
oth oth oth oth oth oth oth oth oth oth oth oth oth oth oth |
| doi_str |
10.1073/pnas.1610921114 |
| up_date |
2024-07-03T23:22:24.577Z |
| _version_ |
1803602042110869504 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a2200265 4500</leader><controlfield tag="001">OLC1989958419</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230715030740.0</controlfield><controlfield tag="007">tu</controlfield><controlfield tag="008">170207s2016 xx ||||| 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1073/pnas.1610921114</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">PQ20170206</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)OLC1989958419</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)GBVOLC1989958419</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(PRQ)c1045-f39e84d25739e8c65faa0ab6a67bad476081f838f307215d3b23bb451e8c266e0</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(KEY)0583363920160000113005108247naddependenttranscriptionalprogramgovernsselfrenew</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">500</subfield><subfield code="q">DNB</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">570</subfield><subfield code="q">AVZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">LING</subfield><subfield code="2">fid</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">BIODIV</subfield><subfield code="2">fid</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Gujar, Amit D</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="3"><subfield code="a">An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2016</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">ohne Hilfsmittel zu benutzen</subfield><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Band</subfield><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD+). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD+ synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival. Pharmacological and genetic inhibition of NAMPT decreased NAD+ levels and GSC self-renewal capacity, and NAMPT knockdown inhibited the in vivo tumorigenicity of GSCs. Regulatory network analysis of RNA sequencing data using GSCs treated with NAMPT inhibitor identified transcription factor E2F2 as the center of a transcriptional hub in the NAD+-dependent network. Accordingly, we demonstrate E2F2 is required for GSC self-renewal. Downstream, E2F2 drives the transcription of members of the inhibitor of differentiation (ID) helix-loop-helix gene family. Finally, we find NAMPT mediates GSC radiation resistance. The identification of a NAMPT-E2F2-ID axis establishes a link between NAD+ metabolism and a self-renewal transcriptional program in glioblastoma, with therapeutic implications for this formidable cancer.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Ribonucleic acid--RNA</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Stem cells</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Correlation analysis</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tumors</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Cancer</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Signal transduction</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Le, Son</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Mao, Diane D</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Dadey, David Y. A</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Turski, Alice</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sasaki, Yo</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Aum, Diane</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Luo, Jingqin</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Dahiya, Sonika</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Yuan, Liya</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Rich, Keith M</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Milbrandt, Jeffrey</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hallahan, Dennis E</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Yano, Hiroko</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tran, David D</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kim, Albert H</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Proceedings of the National Academy of Sciences of the United States of America</subfield><subfield code="d">Washington, DC : NAS, 1877</subfield><subfield code="g">113(2016), 51, Seite E8247-E8256</subfield><subfield code="w">(DE-627)129505269</subfield><subfield code="w">(DE-600)209104-5</subfield><subfield code="w">(DE-576)014909189</subfield><subfield code="x">0027-8424</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:113</subfield><subfield code="g">year:2016</subfield><subfield code="g">number:51</subfield><subfield code="g">pages:E8247-E8256</subfield></datafield><datafield tag="856" ind1="4" ind2="1"><subfield code="u">http://dx.doi.org/10.1073/pnas.1610921114</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://search.proquest.com/docview/1853314761</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_OLC</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">FID-LING</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">FID-BIODIV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHY</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-CHE</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-MAT</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-DE-84</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-MAT</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_59</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">113</subfield><subfield code="j">2016</subfield><subfield code="e">51</subfield><subfield code="h">E8247-E8256</subfield></datafield></record></collection>
|
| score |
7.401578 |