Open AccessTargeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer
Author(s) -
Qian Zhou,
Wensheng Chen,
Zhenzhen Fan,
Zhipeng Chen,
Jinxia Liang,
Guandi Zeng,
Lu Liu,
Wanting Liu,
Tong Yang,
Xin Cao,
Biao Yu,
Meng Xu,
Ye-Guang Chen,
Liang Chen
Publication year - 2021
Publication title -
theranostics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.689
H-Index - 97
ISSN - 1838-7640
DOI - 10.7150/thno.59816
Subject(s) - lung cancer , medicine , cancer research , lung , neuroscience , psychology
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.