TZU-MING JAOWOEI-HORNG FANGSUNG-LIANG YUYu, Sung-LiangSung-LiangYuWeng, Wei TingWei TingWengWeng, Wei-TingWei-TingWengTsai, Ming HongMing HongTsaiTsai, Ming-HongMing-HongTsaiYA-CHIEN YANG2021-03-112021-03-112021-02-280304-3835https://scholars.lib.ntu.edu.tw/handle/123456789/551894Protocadherin 10 (PCDH10) is identified as a tumor suppressor in multiple cancers. The molecular mechanisms that mediate the functions of PCDH10 have yet to be fully elucidated. Here, we demonstrated that ectopic expression of PCDH10 in colorectal cancer (CRC) cells induced cell cycle retardation and increased apoptosis through regulation of the p53/p21/Rb axis and Bcl-2 expression. Overexpression of PCDH10 reversed the epithelial-mesenchymal transition (EMT) process with morphological changes and EMT marker alterations. Mechanistic study revealed that PCDH10 inhibited AKT/GSK3β signaling pathway which in turn reduced β-catenin activity and thus attenuated Snail and Twist1 expression. Furthermore, PCDH10 inhibited the stemness of CRC cells, including spheroid formation and stem cell markers. A proteomics approach revealed that PCDH10 could interact with EGFR, which was further verified by co-immunoprecipitation. Moreover, restoration of PCDH10 expression reduced EGFR phosphorylation. Accordingly, our work proposes a novel pathway by which PCDH10 directly engages in the negative regulation of EGFR/AKT/β-catenin signaling pathway, resulting in tumor suppression.animationCancer stem cell; Epithelial-mesenchymal transition; Protocadherin 10; Signaling pathway[SDGs]SDG3epidermal growth factor receptor; protein kinase B; protein p21; protein p53; protocadherin 10; tumor suppressor protein; unclassified drug; AKT1 protein, human; cadherin; EGFR protein, human; epidermal growth factor receptor; glycogen synthase kinase 3bejournal article10.1016/j.canlet.2020.11.017332712632-s2.0-85097218606WOS:000604424500029https://api.elsevier.com/content/abstract/scopus_id/85097218606