Cargando…
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...
Autores principales: | , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783692008710209536 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8120205 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zhouqian targetinghyperactivetgfbr2fortreatingmyocddeficientlungcancer AT chenwensheng targetinghyperactivetgfbr2fortreatingmyocddeficientlungcancer AT fanzhenzhen targetinghyperactivetgfbr2fortreatingmyocddeficientlungcancer AT chenzhipeng targetinghyperactivetgfbr2fortreatingmyocddeficientlungcancer AT liangjinxia targetinghyperactivetgfbr2fortreatingmyocddeficientlungcancer AT zengguandi targetinghyperactivetgfbr2fortreatingmyocddeficientlungcancer AT liulu targetinghyperactivetgfbr2fortreatingmyocddeficientlungcancer AT liuwanting targetinghyperactivetgfbr2fortreatingmyocddeficientlungcancer AT yangtong targetinghyperactivetgfbr2fortreatingmyocddeficientlungcancer AT caoxin targetinghyperactivetgfbr2fortreatingmyocddeficientlungcancer AT yubiao targetinghyperactivetgfbr2fortreatingmyocddeficientlungcancer AT xumeng targetinghyperactivetgfbr2fortreatingmyocddeficientlungcancer AT chenyeguang targetinghyperactivetgfbr2fortreatingmyocddeficientlungcancer AT chenliang targetinghyperactivetgfbr2fortreatingmyocddeficientlungcancer |