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  • Title: PCDH8 participates in the growth process of colorectal cancer cells by regulating the AKT/GSK3β/β-catenin signaling pathway.
    Author: Wu S, Li X, Yang J, Yang L.
    Journal: Tissue Cell; 2022 Oct; 78():101864. PubMed ID: 35907345.
    Abstract:
    Protocadherin 8 (PCDH8) is lower-expressed in many cancers (gastric cancer, breast cancer, bladder cancer and nasopharyngeal cancer), while the molecular mechanism underlying its effects in human colorectal cancer has not been reported. Therefore, this study aims to investigate the mechanism of PCDH8 in colorectal cancer. After colorectal cancer cells transfected with overexpressing or silencing the gene PCDH8, then the effects of PCDH8 on cell viability, migration, invasion and apoptosis were determined by a series of molecular biological experiments, respectively. The expressions of apoptosis-related factors, AKT/GSK3β/β-catenin signaling pathway- and epithelial-mesenchymal transition (EMT)-related proteins were quantified by western blotting. PCDH8 expression was significantly reduced in the colorectal cancer tissue and cell lines. Overexpressed PCDH8 significantly reduced the proliferation, migration and invasion of colorectal cancer cells, while silent PCDH8 had the opposite effects. Moreover, overexpressed PCDH8 could induce apoptosis, significantly down-regulate expressions of B-cell lymphoma-2 (Bcl-2), N-Cadherin and Vimentin but up-regulate those of Bcl-2 associated X (Bax), cleaved caspase-3 and E-Cadherin, whereas the negative regulations on the apoptosis and the expressions of apoptosis- and EMT-related proteins were observed in colorectal cancer cells following the silence of PCDH8. Furthermore, overexpressed PCDH8 significantly inhibited the phosphorylation of AKT and GSK3β, and repressed the expression of β-catenin, while silent PCDH8 had the opposite effects. In short, PCDH8 overexpression inhibits proliferation, invasion, EMT, and induces apoptosis of colorectal cancer cells by regulating AKT/GSK3β/β-catenin signaling pathway.
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