https://scholars.lib.ntu.edu.tw/handle/123456789/551894
標題: | PCDH10 exerts tumor-suppressor functions through modulation of EGFR/AKT axis in colorectal cancer | 作者: | TZU-MING JAO WOEI-HORNG FANG SUNG-LIANG YU Yu, Sung-Liang Weng, Wei Ting Weng, Wei-Ting Tsai, Ming Hong Tsai, Ming-Hong YA-CHIEN YANG |
關鍵字: | Cancer stem cell; Epithelial-mesenchymal transition; Protocadherin 10; Signaling pathway | 公開日期: | 28-二月-2021 | 出版社: | ELSEVIER IRELAND LTD | 卷: | 499 | 起(迄)頁: | 290 | 來源出版物: | Cancer letters | 摘要: | Protocadherin 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/551894 | ISSN: | 0304-3835 | DOI: | 10.1016/j.canlet.2020.11.017 | SDG/關鍵字: | epidermal 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 3be |
顯示於: | 醫學檢驗暨生物技術學系 |
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