33 96

Cited 5 times in

EGFR-Mediated Reactivation of MAPK Signaling Induces Acquired Resistance to GSK2118436 in BRAF V600E-Mutant NSCLC Cell Lines

Authors
 Sung-Moo Kim  ;  Hwan Kim  ;  Kang Won Jang  ;  Min Hwan Kim  ;  Jinyoung Sohn  ;  Mi Ran Yun  ;  Han Na Kang  ;  Chan Woo Kang  ;  Hye Ryun Kim  ;  Sun Min Lim  ;  Yong Wha Moon  ;  Joo Hang Kim  ;  Soonmyung Paik  ;  Byoung Chul Cho 
Citation
 Molecular Cancer Therapeutics, Vol.15(7) : 1627-1636, 2016 
Journal Title
 Molecular Cancer Therapeutics 
ISSN
 1535-7163 
Issue Date
2016
Abstract
Although treatment of BRAF V600E-mutant non-small cell lung cancer (NSCLC(V600E)) with GSK2118436 has shown an encouraging efficacy, most patients develop resistance. To investigate the mechanisms of acquired resistance to GSK2118436 in NSCLC(V600E), we established GSK2118436-resistant (GSR) cells by exposing MV522 NSCLC(V600E) to increasing GSK2118436 concentrations. GSR cells displayed activated EGFR-RAS-CRAF signaling with upregulated EGFR ligands and sustained activation of ERK1/2, but not MEK1/2, in the presence of GSK2118436. Treatment of GSR cells with GSK2118436 enhanced EGFR-mediated RAS activity, leading to the formation of BRAF-CRAF dimers and transactivation of CRAF. Interestingly, sustained activation of ERK1/2 was partly dependent on receptor-interacting protein kinase-2 (RIP2) activity, but not on MEK1/2 activity. Combined BRAF and EGFR inhibition blocked reactivation of ERK signaling and improved efficacy in vitro and in vivo Our findings support the evaluation of combined BRAF and EGFR inhibition in NSCLC(V600E) with acquired resistance to BRAF inhibitors.
Files in This Item:
T201605637.pdf Download
DOI
10.1158/1535-7163.MCT-15-0375
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
Yonsei Authors
김민환(Kim, Min Hwan) ORCID logo https://orcid.org/0000-0002-1595-6342
김주항(Kim, Joo Hang)
김혜련(Kim, Hye Ryun) ORCID logo https://orcid.org/0000-0002-1842-9070
문용화(Moon, Yong Wha)
백순명(Paik, Soon Myung) ORCID logo https://orcid.org/0000-0001-9688-6480
임선민(Lim, Sun Min)
조병철(Cho, Byoung Chul) ORCID logo https://orcid.org/0000-0002-5562-270X
Export
RIS (EndNote)
XLS (Excel)
XML
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/152921
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse