NRG1 is a critical regulator of differentiation in TP63-driven squamous cell carcinoma

Squamous cell carcinomas (SCCs) account for the majority of cancer mortalities. Although TP63 is an established lineage-survival oncogene in SCCs, therapeutic strategies have not been developed to target TP63 or it’s downstream effectors. In this study we demonstrate that TP63 directly regulates NRG...
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Autor*in:	Ganapati V Hegde [verfasserIn] Cecile de la Cruz [verfasserIn] Jennifer M Giltnane [verfasserIn] Lisa Crocker [verfasserIn] Avinashnarayan Venkatanarayan [verfasserIn] Gabriele Schaefer [verfasserIn] Debra Dunlap [verfasserIn] Joerg D Hoeck [verfasserIn] Robert Piskol [verfasserIn] Florian Gnad [verfasserIn] Zora Modrusan [verfasserIn] Frederic J de Sauvage [verfasserIn] Christian W Siebel [verfasserIn] Erica L Jackson [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	NRG1 ERBB3 TP63 squamous cell cancer

Übergeordnetes Werk:	In: eLife - eLife Sciences Publications Ltd, 2013, 8(2019)
Übergeordnetes Werk:	volume:8 ; year:2019

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.7554/eLife.46551

Katalog-ID:	DOAJ032299699

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Indexfelder

author_variant	g v h gvh c d l c cdlc j m g jmg l c lc a v av g s gs d d dd j d h jdh r p rp f g fg z m zm f j d s fjds c w s cws e l j elj
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allfields	10.7554/eLife.46551 doi (DE-627)DOAJ032299699 (DE-599)DOAJ6f4e75535ef4450d90e11913cada4356 DE-627 ger DE-627 rakwb eng QH301-705.5 Ganapati V Hegde verfasserin aut NRG1 is a critical regulator of differentiation in TP63-driven squamous cell carcinoma 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Squamous cell carcinomas (SCCs) account for the majority of cancer mortalities. Although TP63 is an established lineage-survival oncogene in SCCs, therapeutic strategies have not been developed to target TP63 or it’s downstream effectors. In this study we demonstrate that TP63 directly regulates NRG1 expression in human SCC cell lines and that NRG1 is a critical component of the TP63 transcriptional program. Notably, we show that squamous tumors are dependent NRG1 signaling in vivo, in both genetically engineered mouse models and human xenograft models, and demonstrate that inhibition of NRG1 induces keratinization and terminal squamous differentiation of tumor cells, blocking proliferation and inhibiting tumor growth. Together, our findings identify a lineage-specific function of NRG1 in SCCs of diverse anatomic origin. NRG1 ERBB3 TP63 squamous cell cancer Medicine R Science Q Biology (General) Cecile de la Cruz verfasserin aut Jennifer M Giltnane verfasserin aut Lisa Crocker verfasserin aut Avinashnarayan Venkatanarayan verfasserin aut Gabriele Schaefer verfasserin aut Debra Dunlap verfasserin aut Joerg D Hoeck verfasserin aut Robert Piskol verfasserin aut Florian Gnad verfasserin aut Zora Modrusan verfasserin aut Frederic J de Sauvage verfasserin aut Christian W Siebel verfasserin aut Erica L Jackson verfasserin aut In eLife eLife Sciences Publications Ltd, 2013 8(2019) (DE-627)728518384 (DE-600)2687154-3 2050084X nnns volume:8 year:2019 https://doi.org/10.7554/eLife.46551 kostenfrei https://doaj.org/article/6f4e75535ef4450d90e11913cada4356 kostenfrei https://elifesciences.org/articles/46551 kostenfrei https://doaj.org/toc/2050-084X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019
spelling	10.7554/eLife.46551 doi (DE-627)DOAJ032299699 (DE-599)DOAJ6f4e75535ef4450d90e11913cada4356 DE-627 ger DE-627 rakwb eng QH301-705.5 Ganapati V Hegde verfasserin aut NRG1 is a critical regulator of differentiation in TP63-driven squamous cell carcinoma 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Squamous cell carcinomas (SCCs) account for the majority of cancer mortalities. Although TP63 is an established lineage-survival oncogene in SCCs, therapeutic strategies have not been developed to target TP63 or it’s downstream effectors. In this study we demonstrate that TP63 directly regulates NRG1 expression in human SCC cell lines and that NRG1 is a critical component of the TP63 transcriptional program. Notably, we show that squamous tumors are dependent NRG1 signaling in vivo, in both genetically engineered mouse models and human xenograft models, and demonstrate that inhibition of NRG1 induces keratinization and terminal squamous differentiation of tumor cells, blocking proliferation and inhibiting tumor growth. Together, our findings identify a lineage-specific function of NRG1 in SCCs of diverse anatomic origin. NRG1 ERBB3 TP63 squamous cell cancer Medicine R Science Q Biology (General) Cecile de la Cruz verfasserin aut Jennifer M Giltnane verfasserin aut Lisa Crocker verfasserin aut Avinashnarayan Venkatanarayan verfasserin aut Gabriele Schaefer verfasserin aut Debra Dunlap verfasserin aut Joerg D Hoeck verfasserin aut Robert Piskol verfasserin aut Florian Gnad verfasserin aut Zora Modrusan verfasserin aut Frederic J de Sauvage verfasserin aut Christian W Siebel verfasserin aut Erica L Jackson verfasserin aut In eLife eLife Sciences Publications Ltd, 2013 8(2019) (DE-627)728518384 (DE-600)2687154-3 2050084X nnns volume:8 year:2019 https://doi.org/10.7554/eLife.46551 kostenfrei https://doaj.org/article/6f4e75535ef4450d90e11913cada4356 kostenfrei https://elifesciences.org/articles/46551 kostenfrei https://doaj.org/toc/2050-084X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019
allfields_unstemmed	10.7554/eLife.46551 doi (DE-627)DOAJ032299699 (DE-599)DOAJ6f4e75535ef4450d90e11913cada4356 DE-627 ger DE-627 rakwb eng QH301-705.5 Ganapati V Hegde verfasserin aut NRG1 is a critical regulator of differentiation in TP63-driven squamous cell carcinoma 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Squamous cell carcinomas (SCCs) account for the majority of cancer mortalities. Although TP63 is an established lineage-survival oncogene in SCCs, therapeutic strategies have not been developed to target TP63 or it’s downstream effectors. In this study we demonstrate that TP63 directly regulates NRG1 expression in human SCC cell lines and that NRG1 is a critical component of the TP63 transcriptional program. Notably, we show that squamous tumors are dependent NRG1 signaling in vivo, in both genetically engineered mouse models and human xenograft models, and demonstrate that inhibition of NRG1 induces keratinization and terminal squamous differentiation of tumor cells, blocking proliferation and inhibiting tumor growth. Together, our findings identify a lineage-specific function of NRG1 in SCCs of diverse anatomic origin. NRG1 ERBB3 TP63 squamous cell cancer Medicine R Science Q Biology (General) Cecile de la Cruz verfasserin aut Jennifer M Giltnane verfasserin aut Lisa Crocker verfasserin aut Avinashnarayan Venkatanarayan verfasserin aut Gabriele Schaefer verfasserin aut Debra Dunlap verfasserin aut Joerg D Hoeck verfasserin aut Robert Piskol verfasserin aut Florian Gnad verfasserin aut Zora Modrusan verfasserin aut Frederic J de Sauvage verfasserin aut Christian W Siebel verfasserin aut Erica L Jackson verfasserin aut In eLife eLife Sciences Publications Ltd, 2013 8(2019) (DE-627)728518384 (DE-600)2687154-3 2050084X nnns volume:8 year:2019 https://doi.org/10.7554/eLife.46551 kostenfrei https://doaj.org/article/6f4e75535ef4450d90e11913cada4356 kostenfrei https://elifesciences.org/articles/46551 kostenfrei https://doaj.org/toc/2050-084X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019
allfieldsGer	10.7554/eLife.46551 doi (DE-627)DOAJ032299699 (DE-599)DOAJ6f4e75535ef4450d90e11913cada4356 DE-627 ger DE-627 rakwb eng QH301-705.5 Ganapati V Hegde verfasserin aut NRG1 is a critical regulator of differentiation in TP63-driven squamous cell carcinoma 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Squamous cell carcinomas (SCCs) account for the majority of cancer mortalities. Although TP63 is an established lineage-survival oncogene in SCCs, therapeutic strategies have not been developed to target TP63 or it’s downstream effectors. In this study we demonstrate that TP63 directly regulates NRG1 expression in human SCC cell lines and that NRG1 is a critical component of the TP63 transcriptional program. Notably, we show that squamous tumors are dependent NRG1 signaling in vivo, in both genetically engineered mouse models and human xenograft models, and demonstrate that inhibition of NRG1 induces keratinization and terminal squamous differentiation of tumor cells, blocking proliferation and inhibiting tumor growth. Together, our findings identify a lineage-specific function of NRG1 in SCCs of diverse anatomic origin. NRG1 ERBB3 TP63 squamous cell cancer Medicine R Science Q Biology (General) Cecile de la Cruz verfasserin aut Jennifer M Giltnane verfasserin aut Lisa Crocker verfasserin aut Avinashnarayan Venkatanarayan verfasserin aut Gabriele Schaefer verfasserin aut Debra Dunlap verfasserin aut Joerg D Hoeck verfasserin aut Robert Piskol verfasserin aut Florian Gnad verfasserin aut Zora Modrusan verfasserin aut Frederic J de Sauvage verfasserin aut Christian W Siebel verfasserin aut Erica L Jackson verfasserin aut In eLife eLife Sciences Publications Ltd, 2013 8(2019) (DE-627)728518384 (DE-600)2687154-3 2050084X nnns volume:8 year:2019 https://doi.org/10.7554/eLife.46551 kostenfrei https://doaj.org/article/6f4e75535ef4450d90e11913cada4356 kostenfrei https://elifesciences.org/articles/46551 kostenfrei https://doaj.org/toc/2050-084X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019
allfieldsSound	10.7554/eLife.46551 doi (DE-627)DOAJ032299699 (DE-599)DOAJ6f4e75535ef4450d90e11913cada4356 DE-627 ger DE-627 rakwb eng QH301-705.5 Ganapati V Hegde verfasserin aut NRG1 is a critical regulator of differentiation in TP63-driven squamous cell carcinoma 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Squamous cell carcinomas (SCCs) account for the majority of cancer mortalities. Although TP63 is an established lineage-survival oncogene in SCCs, therapeutic strategies have not been developed to target TP63 or it’s downstream effectors. In this study we demonstrate that TP63 directly regulates NRG1 expression in human SCC cell lines and that NRG1 is a critical component of the TP63 transcriptional program. Notably, we show that squamous tumors are dependent NRG1 signaling in vivo, in both genetically engineered mouse models and human xenograft models, and demonstrate that inhibition of NRG1 induces keratinization and terminal squamous differentiation of tumor cells, blocking proliferation and inhibiting tumor growth. Together, our findings identify a lineage-specific function of NRG1 in SCCs of diverse anatomic origin. NRG1 ERBB3 TP63 squamous cell cancer Medicine R Science Q Biology (General) Cecile de la Cruz verfasserin aut Jennifer M Giltnane verfasserin aut Lisa Crocker verfasserin aut Avinashnarayan Venkatanarayan verfasserin aut Gabriele Schaefer verfasserin aut Debra Dunlap verfasserin aut Joerg D Hoeck verfasserin aut Robert Piskol verfasserin aut Florian Gnad verfasserin aut Zora Modrusan verfasserin aut Frederic J de Sauvage verfasserin aut Christian W Siebel verfasserin aut Erica L Jackson verfasserin aut In eLife eLife Sciences Publications Ltd, 2013 8(2019) (DE-627)728518384 (DE-600)2687154-3 2050084X nnns volume:8 year:2019 https://doi.org/10.7554/eLife.46551 kostenfrei https://doaj.org/article/6f4e75535ef4450d90e11913cada4356 kostenfrei https://elifesciences.org/articles/46551 kostenfrei https://doaj.org/toc/2050-084X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2019
language	English
source	In eLife 8(2019) volume:8 year:2019
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topic_facet	NRG1 ERBB3 TP63 squamous cell cancer Medicine R Science Q Biology (General)
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container_title	eLife
authorswithroles_txt_mv	Ganapati V Hegde @@aut@@ Cecile de la Cruz @@aut@@ Jennifer M Giltnane @@aut@@ Lisa Crocker @@aut@@ Avinashnarayan Venkatanarayan @@aut@@ Gabriele Schaefer @@aut@@ Debra Dunlap @@aut@@ Joerg D Hoeck @@aut@@ Robert Piskol @@aut@@ Florian Gnad @@aut@@ Zora Modrusan @@aut@@ Frederic J de Sauvage @@aut@@ Christian W Siebel @@aut@@ Erica L Jackson @@aut@@
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callnumber-first	Q - Science
author	Ganapati V Hegde
spellingShingle	Ganapati V Hegde misc QH301-705.5 misc NRG1 misc ERBB3 misc TP63 misc squamous cell cancer misc Medicine misc R misc Science misc Q misc Biology (General) NRG1 is a critical regulator of differentiation in TP63-driven squamous cell carcinoma
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topic_title	QH301-705.5 NRG1 is a critical regulator of differentiation in TP63-driven squamous cell carcinoma NRG1 ERBB3 TP63 squamous cell cancer
topic	misc QH301-705.5 misc NRG1 misc ERBB3 misc TP63 misc squamous cell cancer misc Medicine misc R misc Science misc Q misc Biology (General)
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title	NRG1 is a critical regulator of differentiation in TP63-driven squamous cell carcinoma
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title_full	NRG1 is a critical regulator of differentiation in TP63-driven squamous cell carcinoma
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author_browse	Ganapati V Hegde Cecile de la Cruz Jennifer M Giltnane Lisa Crocker Avinashnarayan Venkatanarayan Gabriele Schaefer Debra Dunlap Joerg D Hoeck Robert Piskol Florian Gnad Zora Modrusan Frederic J de Sauvage Christian W Siebel Erica L Jackson
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title_sort	nrg1 is a critical regulator of differentiation in tp63-driven squamous cell carcinoma
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title_auth	NRG1 is a critical regulator of differentiation in TP63-driven squamous cell carcinoma
abstract	Squamous cell carcinomas (SCCs) account for the majority of cancer mortalities. Although TP63 is an established lineage-survival oncogene in SCCs, therapeutic strategies have not been developed to target TP63 or it’s downstream effectors. In this study we demonstrate that TP63 directly regulates NRG1 expression in human SCC cell lines and that NRG1 is a critical component of the TP63 transcriptional program. Notably, we show that squamous tumors are dependent NRG1 signaling in vivo, in both genetically engineered mouse models and human xenograft models, and demonstrate that inhibition of NRG1 induces keratinization and terminal squamous differentiation of tumor cells, blocking proliferation and inhibiting tumor growth. Together, our findings identify a lineage-specific function of NRG1 in SCCs of diverse anatomic origin.
abstractGer	Squamous cell carcinomas (SCCs) account for the majority of cancer mortalities. Although TP63 is an established lineage-survival oncogene in SCCs, therapeutic strategies have not been developed to target TP63 or it’s downstream effectors. In this study we demonstrate that TP63 directly regulates NRG1 expression in human SCC cell lines and that NRG1 is a critical component of the TP63 transcriptional program. Notably, we show that squamous tumors are dependent NRG1 signaling in vivo, in both genetically engineered mouse models and human xenograft models, and demonstrate that inhibition of NRG1 induces keratinization and terminal squamous differentiation of tumor cells, blocking proliferation and inhibiting tumor growth. Together, our findings identify a lineage-specific function of NRG1 in SCCs of diverse anatomic origin.
abstract_unstemmed	Squamous cell carcinomas (SCCs) account for the majority of cancer mortalities. Although TP63 is an established lineage-survival oncogene in SCCs, therapeutic strategies have not been developed to target TP63 or it’s downstream effectors. In this study we demonstrate that TP63 directly regulates NRG1 expression in human SCC cell lines and that NRG1 is a critical component of the TP63 transcriptional program. Notably, we show that squamous tumors are dependent NRG1 signaling in vivo, in both genetically engineered mouse models and human xenograft models, and demonstrate that inhibition of NRG1 induces keratinization and terminal squamous differentiation of tumor cells, blocking proliferation and inhibiting tumor growth. Together, our findings identify a lineage-specific function of NRG1 in SCCs of diverse anatomic origin.
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title_short	NRG1 is a critical regulator of differentiation in TP63-driven squamous cell carcinoma
url	https://doi.org/10.7554/eLife.46551 https://doaj.org/article/6f4e75535ef4450d90e11913cada4356 https://elifesciences.org/articles/46551 https://doaj.org/toc/2050-084X
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up_date	2024-07-04T00:42:33.509Z
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NRG1 is a critical regulator of differentiation in TP63-driven squamous cell carcinoma

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