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Targeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer

Purpose: Clinical success of cancer therapy is severely limited by drug resistance, attributed in large part to the loss of function of tumor suppressor genes (TSGs). Developing effective strategies to treat those tumors is challenging, but urgently needed in clinic. Experimental Design: MYOCD is a...

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Autores principales: Zhou, Qian, Chen, Wensheng, Fan, Zhenzhen, Chen, Zhipeng, Liang, Jinxia, Zeng, Guandi, Liu, Lu, Liu, Wanting, Yang, Tong, Cao, Xin, Yu, Biao, Xu, Meng, Chen, Ye-Guang, Chen, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120205/
https://www.ncbi.nlm.nih.gov/pubmed/33995678
http://dx.doi.org/10.7150/thno.59816
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author Zhou, Qian
Chen, Wensheng
Fan, Zhenzhen
Chen, Zhipeng
Liang, Jinxia
Zeng, Guandi
Liu, Lu
Liu, Wanting
Yang, Tong
Cao, Xin
Yu, Biao
Xu, Meng
Chen, Ye-Guang
Chen, Liang
author_facet Zhou, Qian
Chen, Wensheng
Fan, Zhenzhen
Chen, Zhipeng
Liang, Jinxia
Zeng, Guandi
Liu, Lu
Liu, Wanting
Yang, Tong
Cao, Xin
Yu, Biao
Xu, Meng
Chen, Ye-Guang
Chen, Liang
author_sort Zhou, Qian
collection PubMed
description Purpose: Clinical success of cancer therapy is severely limited by drug resistance, attributed in large part to the loss of function of tumor suppressor genes (TSGs). Developing effective strategies to treat those tumors is challenging, but urgently needed in clinic. Experimental Design: MYOCD is a clinically relevant TSG in lung cancer patients. Our in vitro and in vivo data confirm its tumor suppressive function. Further analysis reveals that MYOCD potently inhibits stemness of lung cancer stem cells. Mechanistically, MYOCD localizes to TGFBR2 promoter region and thereby recruits PRMT5/MEP50 complex to epigenetically silence its transcription. Conclusions: NSCLC cells deficient of MYOCD are particularly sensitive to TGFBR kinase inhibitor (TGFBRi). TGFBRi and stemness inhibitor synergize with existing drugs to treat MYOCD deficient lung cancers. Our current work shows that loss of function of MYOCD creates Achilles' heels in lung cancer cells, which might be exploited in clinic.
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spelling pubmed-81202052021-05-15 Targeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer Zhou, Qian Chen, Wensheng Fan, Zhenzhen Chen, Zhipeng Liang, Jinxia Zeng, Guandi Liu, Lu Liu, Wanting Yang, Tong Cao, Xin Yu, Biao Xu, Meng Chen, Ye-Guang Chen, Liang Theranostics Research Paper Purpose: Clinical success of cancer therapy is severely limited by drug resistance, attributed in large part to the loss of function of tumor suppressor genes (TSGs). Developing effective strategies to treat those tumors is challenging, but urgently needed in clinic. Experimental Design: MYOCD is a clinically relevant TSG in lung cancer patients. Our in vitro and in vivo data confirm its tumor suppressive function. Further analysis reveals that MYOCD potently inhibits stemness of lung cancer stem cells. Mechanistically, MYOCD localizes to TGFBR2 promoter region and thereby recruits PRMT5/MEP50 complex to epigenetically silence its transcription. Conclusions: NSCLC cells deficient of MYOCD are particularly sensitive to TGFBR kinase inhibitor (TGFBRi). TGFBRi and stemness inhibitor synergize with existing drugs to treat MYOCD deficient lung cancers. Our current work shows that loss of function of MYOCD creates Achilles' heels in lung cancer cells, which might be exploited in clinic. Ivyspring International Publisher 2021-05-03 /pmc/articles/PMC8120205/ /pubmed/33995678 http://dx.doi.org/10.7150/thno.59816 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Zhou, Qian
Chen, Wensheng
Fan, Zhenzhen
Chen, Zhipeng
Liang, Jinxia
Zeng, Guandi
Liu, Lu
Liu, Wanting
Yang, Tong
Cao, Xin
Yu, Biao
Xu, Meng
Chen, Ye-Guang
Chen, Liang
Targeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer
title Targeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer
title_full Targeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer
title_fullStr Targeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer
title_full_unstemmed Targeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer
title_short Targeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer
title_sort targeting hyperactive tgfbr2 for treating myocd deficient lung cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120205/
https://www.ncbi.nlm.nih.gov/pubmed/33995678
http://dx.doi.org/10.7150/thno.59816
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