0 6

Cited 0 times in

Loss of desmoglein-2 promotes gallbladder carcinoma progression and resistance to EGFR-targeted therapy through Src kinase activation

Authors
 Sang-Hyun Lee  ;  Jin-Man Kim  ;  Dong Gwang Lee  ;  Jangwook Lee  ;  Jong-Gil Park  ;  Tae-Su Han  ;  Hyun-Soo Cho  ;  Young-Lai Cho  ;  Kwang-Hee Bae  ;  Young-Jun Park  ;  Seon-Jin Lee  ;  Moo-Seung Lee  ;  Yong-Min Huh  ;  Deog Yeon Jo  ;  Hwan-Jung Yun  ;  Heung Jin Jeon  ;  Nayoung Kim  ;  Mina Joo  ;  Jang-Seong Kim  ;  Hyo Jin Lee  ;  Jeong-Ki Min 
Citation
 CELL DEATH AND DIFFERENTIATION, Vol.28(3) : 968-984, 2021-03 
Journal Title
 CELL DEATH AND DIFFERENTIATION 
ISSN
 1350-9047 
Issue Date
2021-03
Abstract
Gallbladder carcinoma (GBC) exhibits poor prognosis due to local recurrence, metastasis, and resistance to targeted therapies. Using clinicopathological analyses of GBC patients along with molecular in vitro and tumor in vivo analysis of GBC cells, we showed that reduction of Dsg2 expression was highly associated with higher T stage, more perineural, and lymphatic invasion. Dsg2-depleted GBC cells exhibited significantly enhanced proliferation, migration, and invasiveness in vitro and tumor growth and metastasis in vivo through Src-mediated signaling activation. Interestingly, Dsg2 binding inhibited Src activation, whereas its loss activated cSrc-mediated EGFR plasma membrane clearance and cytoplasmic localization, which was associated with acquired EGFR-targeted therapy resistance and decreased overall survival. Inhibition of Src activity by dasatinib enhanced therapeutic response to anti-EGFR therapy. Dsg2 status can help stratify predicted patient response to anti-EGFR therapy and Src inhibition could be a promising strategy to improve the clinical efficacy of EGFR-targeted therapy.
DOI
10.1038/s41418-020-00628-4
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Huh, Yong Min(허용민) ORCID logo https://orcid.org/0000-0002-9831-4475
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182229
사서에게 알리기
  feedback

qrcode

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

Browse

Links