癌症研究
蛋白激酶B
PI3K/AKT/mTOR通路
磷酸化
结直肠癌
生物
信号转导
异位表达
细胞生物学
抑制器
上皮-间质转换
Wnt信号通路
化学
癌症
细胞培养
转移
遗传学
作者
Tzu-Ming Jao,Wen‐Hsien Fang,Shih‐Ci Ciou,Shan‐Fu Yu,Yu-Lin Hung,Wei-Ting Weng,Tsai-Yi Lin,Ming‐Hong Tsai,Ya-Chien Yang
标识
DOI:10.1016/j.canlet.2020.11.017
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI