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Cell Res. 2015 Apr;25(4):445-58. doi: 10.1038/cr.2015.16. Epub 2015 Feb 6.

SMARCE1 suppresses EGFR expression and controls responses to MET and ALK inhibitors in lung cancer.

Author information

1
Department of Biochemistry, The Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, QC H3G 1Y6, Canada.
2
Division of Molecular Carcinogenesis, Cancer Systems Biology Centre and Cancer Genomics Centre, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
3
1] Division of Molecular Carcinogenesis, Cancer Systems Biology Centre and Cancer Genomics Centre, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands [2] Institute for Systems Biology, 401 Terry Avenue North, Seattle, WA 98109-5234, USA.
4
1] Division of Molecular Carcinogenesis, Cancer Systems Biology Centre and Cancer Genomics Centre, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands [2] Current address: Unit for RNA Biology, Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, 53105 Bonn, Germany.

Abstract

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.

PMID:
25656847
PMCID:
PMC4387553
DOI:
10.1038/cr.2015.16
[Indexed for MEDLINE]
Free PMC Article

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