Targeting glypican-4 overcomes 5-FU resistance and attenuates stem cell-like properties via suppression of Wnt/β-catenin pathway in pancreatic cancer cells

Journal of Cellular Biochemistry
Junyu CaoLiang Han

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 st...Continue Reading

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Citations

Sep 5, 2019·International Journal of Molecular Sciences·Monish Ram MakenaKartick C Pramanik
Jul 7, 2020·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Nan LiMitchell Ho
Jul 25, 2019·Frontiers in Cell and Developmental Biology·Sameera NallanthighalDong-Joo Cheon
Sep 13, 2020·International Journal of Molecular Sciences·Valeria De Pasquale, Luigi Michele Pavone
Jun 30, 2019·Biochemical Pharmacology·Sukhneeraj P Kaur, Brian S Cummings
Dec 18, 2020·Frontiers in Cell and Developmental Biology·Maanasa RavikumarSimon M Cool
Jan 24, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Chinmayee Sethy, Chanakya Nath Kundu
Oct 26, 2018·Trends in Cancer·Nan LiMitchell Ho
Jul 13, 2021·Frontiers in Oncology·Simone Furini, Chiara Falciani
Aug 29, 2021·Cancer Metastasis Reviews·Kalyani PatilShahab Uddin

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