Premium
Targeting glypican‐4 overcomes 5‐FU resistance and attenuates stem cell–like properties via suppression of Wnt/β‐catenin pathway in pancreatic cancer cells
Author(s) -
Cao Junyu,
Ma Jiguang,
Sun Liankang,
Li Jie,
Qin Tao,
Zhou Cancan,
Cheng Liang,
Chen Ke,
Qian Weikun,
Duan Wanxing,
Wang Fengfei,
Wu Erxi,
Wang Zheng,
Ma Qingyong,
Han Liang
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27266
Subject(s) - pancreatic cancer , wnt signaling pathway , cancer research , gene knockdown , biology , cancer , cancer stem cell , catenin , cancer cell , cell culture , microbiology and biotechnology , genetics , signal transduction
The existences of cancer stem cells in patients with pancreatic cancer are considered as pivotal factors contributing to chemoresistance and disease relapse. Glypican‐4 (GPC4) is one of the members of the glypicans family, which underlies human congenital malformations and multiple diseases. However, its potential biological function in pancreatic cancer still remains elusive. In this study, we are the first to demonstrate that GPC4 was involved in 5‐fluorouracil (5‐FU) resistance and pancreatic cancer stemness through comprehensive bioinformatical analysis. Functional experiments showed that knockdown of GPC4 sensitized pancreatic cancer cells to 5‐FU and attenuated stem cell–like properties. In terms of mechanism research, knockdown of GPC4 suppressed the activation of Wnt/β‐catenin pathway and its downstream targets. Furthermore, the expression of GPC4 was significantly upregulated in pancreatic cancer tissues compared with normal tissues and remarkably correlated with patients’ overall survival according to the data derived from the Cancer Genome Atlas database. Taken together, our results suggest that GPC4 is a key regulator in chemoresistance and pancreatic cancer stemness. Thus, targeting GPC4 may serve as a promising strategy for pancreatic cancer therapy.