期刊
CELL RESEARCH
卷 25, 期 4, 页码 445-458出版社
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2015.16
关键词
EGFR signaling; drug resistance; RNAi screening; SMARCE1; SWI/SNF
类别
资金
- Canadian Institutes of Health Research (CIHR) [MOP-130540]
- Canada Research Chair (CRC)
- European Research Council (ERC)
- Dutch Cancer Society (KWF)
- EU COLTHERES project
- Netherlands Organization for Scientific Research (NWO) to the Cancer Genomics Center Netherlands (CGC.NL)
- Cancer System Biology Center (CSBC)
- CIHR - McGill Chemical Biology Postdoctoral Fellowship Award
- CRC in Functional Genomics
Recurrent inactivating mutations in components of SWI/SNF chromatin-remodeling complexes have been identified across cancer types, supporting their roles as tumor suppressors in modulating oncogenic signaling pathways. We report here that SMARCE1 loss induces EGFR expression and confers resistance to MET and ALK inhibitors in non-small cell lung cancers (NSCLCs). We found that SMARCE1 binds to regulatory regions of the EGFR locus and suppresses EGFR transcription in part through regulating expression of Polycomb Repressive Complex component CBX2. Addition of the EGFR inhibitor gefitinib restores the sensitivity of SMARCE1-knockdown cells to MET and ALK inhibitors in NSCLCs. Our findings link SMARCE1 to EGFR oncogenic signaling and suggest targeted treatment options for SMARCE1-deficient tumors.
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