Targeting glypican‐4 overcomes 5‐FU resistance and attenuates stem cell–like properties via suppression of Wnt/β‐catenin pathway in pancreatic cancer cells. Issue 11 (16th July 2018)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Journal of cellular biochemistry. Volume 119:Issue 11(2018)
• Page Start: 9498
• Page End: 9512
• Publication Date: 2018-07-16
• Subjects: 5‐FU resistance -- bioinformatical analysis -- glypican‐4 (GPC4) -- pancreatic cancer -- stem cell–like properties -- Wnt/β‐catenin pathway; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.27266
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: 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. Abstract : Glypican‐4(GPC4) regulates 5‐FU resistance and stem cell–like properties of pancreatic cancer cells. Inhibition of glypican‐4 suppresses Wnt/β‐catenin pathway.Glypican‐4 is upregulated in pancreatic cancer and associated with overall survival.