A chemical probe of CARM1 alters epigenetic plasticity against breast cancer cell invasion

CARM1 is a cancer-relevant protein arginine methyltransferase that regulates many aspects of transcription. Its pharmacological inhibition is a promising anti-cancer strategy. Here SKI-73 (6a in this work) is presented as a CARM1 chemical probe with pro-drug properties. SKI-73 (6a) can rapidly penet...
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Autor*in:	Xiao-Chuan Cai [verfasserIn] Tuo Zhang [verfasserIn] Eui-jun Kim [verfasserIn] Ming Jiang [verfasserIn] Ke Wang [verfasserIn] Junyi Wang [verfasserIn] Shi Chen [verfasserIn] Nawei Zhang [verfasserIn] Hong Wu [verfasserIn] Fengling Li [verfasserIn] Carlo C dela Seña [verfasserIn] Hong Zeng [verfasserIn] Victor Vivcharuk [verfasserIn] Xiang Niu [verfasserIn] Weihong Zheng [verfasserIn] Jonghan P Lee [verfasserIn] Yuling Chen [verfasserIn] Dalia Barsyte [verfasserIn] Magda Szewczyk [verfasserIn] Taraneh Hajian [verfasserIn] Glorymar Ibáñez [verfasserIn] Aiping Dong [verfasserIn] Ludmila Dombrovski [verfasserIn] Zhenyu Zhang [verfasserIn] Haiteng Deng [verfasserIn] Jinrong Min [verfasserIn] Cheryl H Arrowsmith [verfasserIn] Linas Mazutis [verfasserIn] Lei Shi [verfasserIn] Masoud Vedadi [verfasserIn] Peter J Brown [verfasserIn] Jenny Xiang [verfasserIn] Li-Xuan Qin [verfasserIn] Wei Xu [verfasserIn] Minkui Luo [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	PRMT methylation epigenetic inhibitor single cell mechanism

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.47110

Katalog-ID:	DOAJ005652464

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allfields	10.7554/eLife.47110 doi (DE-627)DOAJ005652464 (DE-599)DOAJe2cc04f7ee7c46688f502928eba49e93 DE-627 ger DE-627 rakwb eng QH301-705.5 Xiao-Chuan Cai verfasserin aut A chemical probe of CARM1 alters epigenetic plasticity against breast cancer cell invasion 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier CARM1 is a cancer-relevant protein arginine methyltransferase that regulates many aspects of transcription. Its pharmacological inhibition is a promising anti-cancer strategy. Here SKI-73 (6a in this work) is presented as a CARM1 chemical probe with pro-drug properties. SKI-73 (6a) can rapidly penetrate cell membranes and then be processed into active inhibitors, which are retained intracellularly with 10-fold enrichment for several days. These compounds were characterized for their potency, selectivity, modes of action, and on-target engagement. SKI-73 (6a) recapitulates the effect of CARM1 knockout against breast cancer cell invasion. Single-cell RNA-seq analysis revealed that the SKI-73(6a)-associated reduction of invasiveness acts by altering epigenetic plasticity and suppressing the invasion-prone subpopulation. Interestingly, SKI-73 (6a) and CARM1 knockout alter the epigenetic plasticity with remarkable difference, suggesting distinct modes of action for small-molecule and genetic perturbations. We therefore discovered a CARM1-addiction mechanism of cancer metastasis and developed a chemical probe to target this process. PRMT methylation epigenetic inhibitor single cell mechanism Medicine R Science Q Biology (General) Tuo Zhang verfasserin aut Eui-jun Kim verfasserin aut Ming Jiang verfasserin aut Ke Wang verfasserin aut Junyi Wang verfasserin aut Shi Chen verfasserin aut Nawei Zhang verfasserin aut Hong Wu verfasserin aut Fengling Li verfasserin aut Carlo C dela Seña verfasserin aut Hong Zeng verfasserin aut Victor Vivcharuk verfasserin aut Xiang Niu verfasserin aut Weihong Zheng verfasserin aut Jonghan P Lee verfasserin aut Yuling Chen verfasserin aut Dalia Barsyte verfasserin aut Magda Szewczyk verfasserin aut Taraneh Hajian verfasserin aut Glorymar Ibáñez verfasserin aut Aiping Dong verfasserin aut Ludmila Dombrovski verfasserin aut Zhenyu Zhang verfasserin aut Haiteng Deng verfasserin aut Jinrong Min verfasserin aut Cheryl H Arrowsmith verfasserin aut Linas Mazutis verfasserin aut Lei Shi verfasserin aut Masoud Vedadi verfasserin aut Peter J Brown verfasserin aut Jenny Xiang verfasserin aut Li-Xuan Qin verfasserin aut Wei Xu verfasserin aut Minkui Luo 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.47110 kostenfrei https://doaj.org/article/e2cc04f7ee7c46688f502928eba49e93 kostenfrei https://elifesciences.org/articles/47110 kostenfrei https://doaj.org/toc/2050-084X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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.47110 doi (DE-627)DOAJ005652464 (DE-599)DOAJe2cc04f7ee7c46688f502928eba49e93 DE-627 ger DE-627 rakwb eng QH301-705.5 Xiao-Chuan Cai verfasserin aut A chemical probe of CARM1 alters epigenetic plasticity against breast cancer cell invasion 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier CARM1 is a cancer-relevant protein arginine methyltransferase that regulates many aspects of transcription. Its pharmacological inhibition is a promising anti-cancer strategy. Here SKI-73 (6a in this work) is presented as a CARM1 chemical probe with pro-drug properties. SKI-73 (6a) can rapidly penetrate cell membranes and then be processed into active inhibitors, which are retained intracellularly with 10-fold enrichment for several days. These compounds were characterized for their potency, selectivity, modes of action, and on-target engagement. SKI-73 (6a) recapitulates the effect of CARM1 knockout against breast cancer cell invasion. Single-cell RNA-seq analysis revealed that the SKI-73(6a)-associated reduction of invasiveness acts by altering epigenetic plasticity and suppressing the invasion-prone subpopulation. Interestingly, SKI-73 (6a) and CARM1 knockout alter the epigenetic plasticity with remarkable difference, suggesting distinct modes of action for small-molecule and genetic perturbations. We therefore discovered a CARM1-addiction mechanism of cancer metastasis and developed a chemical probe to target this process. PRMT methylation epigenetic inhibitor single cell mechanism Medicine R Science Q Biology (General) Tuo Zhang verfasserin aut Eui-jun Kim verfasserin aut Ming Jiang verfasserin aut Ke Wang verfasserin aut Junyi Wang verfasserin aut Shi Chen verfasserin aut Nawei Zhang verfasserin aut Hong Wu verfasserin aut Fengling Li verfasserin aut Carlo C dela Seña verfasserin aut Hong Zeng verfasserin aut Victor Vivcharuk verfasserin aut Xiang Niu verfasserin aut Weihong Zheng verfasserin aut Jonghan P Lee verfasserin aut Yuling Chen verfasserin aut Dalia Barsyte verfasserin aut Magda Szewczyk verfasserin aut Taraneh Hajian verfasserin aut Glorymar Ibáñez verfasserin aut Aiping Dong verfasserin aut Ludmila Dombrovski verfasserin aut Zhenyu Zhang verfasserin aut Haiteng Deng verfasserin aut Jinrong Min verfasserin aut Cheryl H Arrowsmith verfasserin aut Linas Mazutis verfasserin aut Lei Shi verfasserin aut Masoud Vedadi verfasserin aut Peter J Brown verfasserin aut Jenny Xiang verfasserin aut Li-Xuan Qin verfasserin aut Wei Xu verfasserin aut Minkui Luo 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.47110 kostenfrei https://doaj.org/article/e2cc04f7ee7c46688f502928eba49e93 kostenfrei https://elifesciences.org/articles/47110 kostenfrei https://doaj.org/toc/2050-084X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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.47110 doi (DE-627)DOAJ005652464 (DE-599)DOAJe2cc04f7ee7c46688f502928eba49e93 DE-627 ger DE-627 rakwb eng QH301-705.5 Xiao-Chuan Cai verfasserin aut A chemical probe of CARM1 alters epigenetic plasticity against breast cancer cell invasion 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier CARM1 is a cancer-relevant protein arginine methyltransferase that regulates many aspects of transcription. Its pharmacological inhibition is a promising anti-cancer strategy. Here SKI-73 (6a in this work) is presented as a CARM1 chemical probe with pro-drug properties. SKI-73 (6a) can rapidly penetrate cell membranes and then be processed into active inhibitors, which are retained intracellularly with 10-fold enrichment for several days. These compounds were characterized for their potency, selectivity, modes of action, and on-target engagement. SKI-73 (6a) recapitulates the effect of CARM1 knockout against breast cancer cell invasion. Single-cell RNA-seq analysis revealed that the SKI-73(6a)-associated reduction of invasiveness acts by altering epigenetic plasticity and suppressing the invasion-prone subpopulation. Interestingly, SKI-73 (6a) and CARM1 knockout alter the epigenetic plasticity with remarkable difference, suggesting distinct modes of action for small-molecule and genetic perturbations. We therefore discovered a CARM1-addiction mechanism of cancer metastasis and developed a chemical probe to target this process. PRMT methylation epigenetic inhibitor single cell mechanism Medicine R Science Q Biology (General) Tuo Zhang verfasserin aut Eui-jun Kim verfasserin aut Ming Jiang verfasserin aut Ke Wang verfasserin aut Junyi Wang verfasserin aut Shi Chen verfasserin aut Nawei Zhang verfasserin aut Hong Wu verfasserin aut Fengling Li verfasserin aut Carlo C dela Seña verfasserin aut Hong Zeng verfasserin aut Victor Vivcharuk verfasserin aut Xiang Niu verfasserin aut Weihong Zheng verfasserin aut Jonghan P Lee verfasserin aut Yuling Chen verfasserin aut Dalia Barsyte verfasserin aut Magda Szewczyk verfasserin aut Taraneh Hajian verfasserin aut Glorymar Ibáñez verfasserin aut Aiping Dong verfasserin aut Ludmila Dombrovski verfasserin aut Zhenyu Zhang verfasserin aut Haiteng Deng verfasserin aut Jinrong Min verfasserin aut Cheryl H Arrowsmith verfasserin aut Linas Mazutis verfasserin aut Lei Shi verfasserin aut Masoud Vedadi verfasserin aut Peter J Brown verfasserin aut Jenny Xiang verfasserin aut Li-Xuan Qin verfasserin aut Wei Xu verfasserin aut Minkui Luo 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.47110 kostenfrei https://doaj.org/article/e2cc04f7ee7c46688f502928eba49e93 kostenfrei https://elifesciences.org/articles/47110 kostenfrei https://doaj.org/toc/2050-084X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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.47110 doi (DE-627)DOAJ005652464 (DE-599)DOAJe2cc04f7ee7c46688f502928eba49e93 DE-627 ger DE-627 rakwb eng QH301-705.5 Xiao-Chuan Cai verfasserin aut A chemical probe of CARM1 alters epigenetic plasticity against breast cancer cell invasion 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier CARM1 is a cancer-relevant protein arginine methyltransferase that regulates many aspects of transcription. Its pharmacological inhibition is a promising anti-cancer strategy. Here SKI-73 (6a in this work) is presented as a CARM1 chemical probe with pro-drug properties. SKI-73 (6a) can rapidly penetrate cell membranes and then be processed into active inhibitors, which are retained intracellularly with 10-fold enrichment for several days. These compounds were characterized for their potency, selectivity, modes of action, and on-target engagement. SKI-73 (6a) recapitulates the effect of CARM1 knockout against breast cancer cell invasion. Single-cell RNA-seq analysis revealed that the SKI-73(6a)-associated reduction of invasiveness acts by altering epigenetic plasticity and suppressing the invasion-prone subpopulation. Interestingly, SKI-73 (6a) and CARM1 knockout alter the epigenetic plasticity with remarkable difference, suggesting distinct modes of action for small-molecule and genetic perturbations. We therefore discovered a CARM1-addiction mechanism of cancer metastasis and developed a chemical probe to target this process. PRMT methylation epigenetic inhibitor single cell mechanism Medicine R Science Q Biology (General) Tuo Zhang verfasserin aut Eui-jun Kim verfasserin aut Ming Jiang verfasserin aut Ke Wang verfasserin aut Junyi Wang verfasserin aut Shi Chen verfasserin aut Nawei Zhang verfasserin aut Hong Wu verfasserin aut Fengling Li verfasserin aut Carlo C dela Seña verfasserin aut Hong Zeng verfasserin aut Victor Vivcharuk verfasserin aut Xiang Niu verfasserin aut Weihong Zheng verfasserin aut Jonghan P Lee verfasserin aut Yuling Chen verfasserin aut Dalia Barsyte verfasserin aut Magda Szewczyk verfasserin aut Taraneh Hajian verfasserin aut Glorymar Ibáñez verfasserin aut Aiping Dong verfasserin aut Ludmila Dombrovski verfasserin aut Zhenyu Zhang verfasserin aut Haiteng Deng verfasserin aut Jinrong Min verfasserin aut Cheryl H Arrowsmith verfasserin aut Linas Mazutis verfasserin aut Lei Shi verfasserin aut Masoud Vedadi verfasserin aut Peter J Brown verfasserin aut Jenny Xiang verfasserin aut Li-Xuan Qin verfasserin aut Wei Xu verfasserin aut Minkui Luo 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.47110 kostenfrei https://doaj.org/article/e2cc04f7ee7c46688f502928eba49e93 kostenfrei https://elifesciences.org/articles/47110 kostenfrei https://doaj.org/toc/2050-084X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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.47110 doi (DE-627)DOAJ005652464 (DE-599)DOAJe2cc04f7ee7c46688f502928eba49e93 DE-627 ger DE-627 rakwb eng QH301-705.5 Xiao-Chuan Cai verfasserin aut A chemical probe of CARM1 alters epigenetic plasticity against breast cancer cell invasion 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier CARM1 is a cancer-relevant protein arginine methyltransferase that regulates many aspects of transcription. Its pharmacological inhibition is a promising anti-cancer strategy. Here SKI-73 (6a in this work) is presented as a CARM1 chemical probe with pro-drug properties. SKI-73 (6a) can rapidly penetrate cell membranes and then be processed into active inhibitors, which are retained intracellularly with 10-fold enrichment for several days. These compounds were characterized for their potency, selectivity, modes of action, and on-target engagement. SKI-73 (6a) recapitulates the effect of CARM1 knockout against breast cancer cell invasion. Single-cell RNA-seq analysis revealed that the SKI-73(6a)-associated reduction of invasiveness acts by altering epigenetic plasticity and suppressing the invasion-prone subpopulation. Interestingly, SKI-73 (6a) and CARM1 knockout alter the epigenetic plasticity with remarkable difference, suggesting distinct modes of action for small-molecule and genetic perturbations. We therefore discovered a CARM1-addiction mechanism of cancer metastasis and developed a chemical probe to target this process. PRMT methylation epigenetic inhibitor single cell mechanism Medicine R Science Q Biology (General) Tuo Zhang verfasserin aut Eui-jun Kim verfasserin aut Ming Jiang verfasserin aut Ke Wang verfasserin aut Junyi Wang verfasserin aut Shi Chen verfasserin aut Nawei Zhang verfasserin aut Hong Wu verfasserin aut Fengling Li verfasserin aut Carlo C dela Seña verfasserin aut Hong Zeng verfasserin aut Victor Vivcharuk verfasserin aut Xiang Niu verfasserin aut Weihong Zheng verfasserin aut Jonghan P Lee verfasserin aut Yuling Chen verfasserin aut Dalia Barsyte verfasserin aut Magda Szewczyk verfasserin aut Taraneh Hajian verfasserin aut Glorymar Ibáñez verfasserin aut Aiping Dong verfasserin aut Ludmila Dombrovski verfasserin aut Zhenyu Zhang verfasserin aut Haiteng Deng verfasserin aut Jinrong Min verfasserin aut Cheryl H Arrowsmith verfasserin aut Linas Mazutis verfasserin aut Lei Shi verfasserin aut Masoud Vedadi verfasserin aut Peter J Brown verfasserin aut Jenny Xiang verfasserin aut Li-Xuan Qin verfasserin aut Wei Xu verfasserin aut Minkui Luo 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.47110 kostenfrei https://doaj.org/article/e2cc04f7ee7c46688f502928eba49e93 kostenfrei https://elifesciences.org/articles/47110 kostenfrei https://doaj.org/toc/2050-084X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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
sourceStr	In eLife 8(2019) volume:8 year:2019
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	PRMT methylation epigenetic inhibitor single cell mechanism Medicine R Science Q Biology (General)
isfreeaccess_bool	true
container_title	eLife
authorswithroles_txt_mv	Xiao-Chuan Cai @@aut@@ Tuo Zhang @@aut@@ Eui-jun Kim @@aut@@ Ming Jiang @@aut@@ Ke Wang @@aut@@ Junyi Wang @@aut@@ Shi Chen @@aut@@ Nawei Zhang @@aut@@ Hong Wu @@aut@@ Fengling Li @@aut@@ Carlo C dela Seña @@aut@@ Hong Zeng @@aut@@ Victor Vivcharuk @@aut@@ Xiang Niu @@aut@@ Weihong Zheng @@aut@@ Jonghan P Lee @@aut@@ Yuling Chen @@aut@@ Dalia Barsyte @@aut@@ Magda Szewczyk @@aut@@ Taraneh Hajian @@aut@@ Glorymar Ibáñez @@aut@@ Aiping Dong @@aut@@ Ludmila Dombrovski @@aut@@ Zhenyu Zhang @@aut@@ Haiteng Deng @@aut@@ Jinrong Min @@aut@@ Cheryl H Arrowsmith @@aut@@ Linas Mazutis @@aut@@ Lei Shi @@aut@@ Masoud Vedadi @@aut@@ Peter J Brown @@aut@@ Jenny Xiang @@aut@@ Li-Xuan Qin @@aut@@ Wei Xu @@aut@@ Minkui Luo @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
hierarchy_top_id	728518384
id	DOAJ005652464
language_de	englisch
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callnumber-first	Q - Science
author	Xiao-Chuan Cai
spellingShingle	Xiao-Chuan Cai misc QH301-705.5 misc PRMT misc methylation misc epigenetic misc inhibitor misc single cell misc mechanism misc Medicine misc R misc Science misc Q misc Biology (General) A chemical probe of CARM1 alters epigenetic plasticity against breast cancer cell invasion
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topic_title	QH301-705.5 A chemical probe of CARM1 alters epigenetic plasticity against breast cancer cell invasion PRMT methylation epigenetic inhibitor single cell mechanism
topic	misc QH301-705.5 misc PRMT misc methylation misc epigenetic misc inhibitor misc single cell misc mechanism misc Medicine misc R misc Science misc Q misc Biology (General)
topic_unstemmed	misc QH301-705.5 misc PRMT misc methylation misc epigenetic misc inhibitor misc single cell misc mechanism misc Medicine misc R misc Science misc Q misc Biology (General)
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title	A chemical probe of CARM1 alters epigenetic plasticity against breast cancer cell invasion
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title_full	A chemical probe of CARM1 alters epigenetic plasticity against breast cancer cell invasion
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author_browse	Xiao-Chuan Cai Tuo Zhang Eui-jun Kim Ming Jiang Ke Wang Junyi Wang Shi Chen Nawei Zhang Hong Wu Fengling Li Carlo C dela Seña Hong Zeng Victor Vivcharuk Xiang Niu Weihong Zheng Jonghan P Lee Yuling Chen Dalia Barsyte Magda Szewczyk Taraneh Hajian Glorymar Ibáñez Aiping Dong Ludmila Dombrovski Zhenyu Zhang Haiteng Deng Jinrong Min Cheryl H Arrowsmith Linas Mazutis Lei Shi Masoud Vedadi Peter J Brown Jenny Xiang Li-Xuan Qin Wei Xu Minkui Luo
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title_sort	chemical probe of carm1 alters epigenetic plasticity against breast cancer cell invasion
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title_auth	A chemical probe of CARM1 alters epigenetic plasticity against breast cancer cell invasion
abstract	CARM1 is a cancer-relevant protein arginine methyltransferase that regulates many aspects of transcription. Its pharmacological inhibition is a promising anti-cancer strategy. Here SKI-73 (6a in this work) is presented as a CARM1 chemical probe with pro-drug properties. SKI-73 (6a) can rapidly penetrate cell membranes and then be processed into active inhibitors, which are retained intracellularly with 10-fold enrichment for several days. These compounds were characterized for their potency, selectivity, modes of action, and on-target engagement. SKI-73 (6a) recapitulates the effect of CARM1 knockout against breast cancer cell invasion. Single-cell RNA-seq analysis revealed that the SKI-73(6a)-associated reduction of invasiveness acts by altering epigenetic plasticity and suppressing the invasion-prone subpopulation. Interestingly, SKI-73 (6a) and CARM1 knockout alter the epigenetic plasticity with remarkable difference, suggesting distinct modes of action for small-molecule and genetic perturbations. We therefore discovered a CARM1-addiction mechanism of cancer metastasis and developed a chemical probe to target this process.
abstractGer	CARM1 is a cancer-relevant protein arginine methyltransferase that regulates many aspects of transcription. Its pharmacological inhibition is a promising anti-cancer strategy. Here SKI-73 (6a in this work) is presented as a CARM1 chemical probe with pro-drug properties. SKI-73 (6a) can rapidly penetrate cell membranes and then be processed into active inhibitors, which are retained intracellularly with 10-fold enrichment for several days. These compounds were characterized for their potency, selectivity, modes of action, and on-target engagement. SKI-73 (6a) recapitulates the effect of CARM1 knockout against breast cancer cell invasion. Single-cell RNA-seq analysis revealed that the SKI-73(6a)-associated reduction of invasiveness acts by altering epigenetic plasticity and suppressing the invasion-prone subpopulation. Interestingly, SKI-73 (6a) and CARM1 knockout alter the epigenetic plasticity with remarkable difference, suggesting distinct modes of action for small-molecule and genetic perturbations. We therefore discovered a CARM1-addiction mechanism of cancer metastasis and developed a chemical probe to target this process.
abstract_unstemmed	CARM1 is a cancer-relevant protein arginine methyltransferase that regulates many aspects of transcription. Its pharmacological inhibition is a promising anti-cancer strategy. Here SKI-73 (6a in this work) is presented as a CARM1 chemical probe with pro-drug properties. SKI-73 (6a) can rapidly penetrate cell membranes and then be processed into active inhibitors, which are retained intracellularly with 10-fold enrichment for several days. These compounds were characterized for their potency, selectivity, modes of action, and on-target engagement. SKI-73 (6a) recapitulates the effect of CARM1 knockout against breast cancer cell invasion. Single-cell RNA-seq analysis revealed that the SKI-73(6a)-associated reduction of invasiveness acts by altering epigenetic plasticity and suppressing the invasion-prone subpopulation. Interestingly, SKI-73 (6a) and CARM1 knockout alter the epigenetic plasticity with remarkable difference, suggesting distinct modes of action for small-molecule and genetic perturbations. We therefore discovered a CARM1-addiction mechanism of cancer metastasis and developed a chemical probe to target this process.
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title_short	A chemical probe of CARM1 alters epigenetic plasticity against breast cancer cell invasion
url	https://doi.org/10.7554/eLife.47110 https://doaj.org/article/e2cc04f7ee7c46688f502928eba49e93 https://elifesciences.org/articles/47110 https://doaj.org/toc/2050-084X
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