title: TrpC5 regulates differentiation through the Ca2+/Wnt5a signalling pathway in colorectal cancer.
abstract: Transient receptor potential channel 5 (TrpC5) is a member of the TrpC subgroup, and it forms a receptor-activated, non-selective Ca2+channel. The architecture of the TrpC5 channel is poorly understood. In the present study, we report that TrpC5 is a key factor in regulating differentiation in colorectal cancer (CRC). Through a study of specimens from a large cohort of patients with CRC, we found that TrpC5 was highly expressed and its cellular level correlated with tumour grade. We showed further that up-regulated TrpC5 caused a robust rise in intracellular calcium concentration [Ca2+]i, increased Wnt5a expression and the nuclear translocation of β-catenin, leading to a reduction in cancer differentiation and an increase in cancer cell stemness. Notably, patients with tumours that expressed high levels of TrpC5 showed significantly poorer disease-free and overall survival. Therefore, our findings suggest that TrpC5 is an independent adverse prognostic factor for death in CRC, reducing differentiation through the Ca2+/Wnt5a signalling pathway.
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Tang
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
authors.forename: Yaodan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
authors.forename: Mingxu
authors.initials: M
authors.lastname: Xie
authors.affiliation: National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi, China.
authors.forename: Dongxu
authors.initials: D
authors.lastname: He
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
authors.forename: Qiongxi
authors.initials: Q
authors.lastname: Pan
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.|School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Affiliated Hospital, Jiangnan University, Wuxi, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hua
authors.affiliation: Affiliated Hospital, Jiangnan University, Wuxi, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Affiliated Hospital, Jiangnan University, Wuxi, China.
authors.forename: Linfang
authors.initials: L
authors.lastname: Jin
authors.affiliation: Affiliated Hospital, Jiangnan University, Wuxi, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Qi
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yao
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China maxin@jiangnan.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D020013:Calcium Signaling; D002277:Carcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D019073:HT29 Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D060787:Neoplasm Grading; D011379:Prognosis; D050052:TRPC Cation Channels / Q000378:metabolism*; D000071818:Wnt-5a Protein / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D050052:TRPC Cation Channels; C491780:TRPC5 protein, human; C085389:WNT5A protein, human; D000071818:Wnt-5a Protein; D051176:beta Catenin
keywords: Ca2+/Wnt5a signalling pathway; TrpC5 ion channel; cancer cell differentiation; colorectal cancer