General Surgery Department, The Second Affiliated Hospital of Shandong First Medical University, China.
Department of Medical Imaging, The Second Affiliated Hospital of Shandong First Medical University, China.
Tissue Cell. 2022 Oct;78:101864. doi: 10.1016/j.tice.2022.101864. Epub 2022 Jul 4.
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.
原钙黏蛋白 8（PCDH8）在许多癌症（胃癌、乳腺癌、膀胱癌和鼻咽癌）中表达水平较低，但其在人结直肠癌中的作用的分子机制尚未报道。因此，本研究旨在探讨 PCDH8 在结直肠癌中的作用机制。通过转染过表达或沉默基因 PCDH8 的结直肠癌细胞，分别通过一系列分子生物学实验确定 PCDH8 对细胞活力、迁移、侵袭和凋亡的影响。通过蛋白质印迹法定量检测凋亡相关因子、AKT/GSK3β/β-catenin 信号通路和上皮间质转化（EMT）相关蛋白的表达。PCDH8 在结直肠癌组织和细胞系中的表达明显降低。过表达 PCDH8 显著降低结直肠癌细胞的增殖、迁移和侵袭能力，而沉默 PCDH8 则产生相反的效果。此外，过表达 PCDH8 可诱导细胞凋亡，显著下调 B 细胞淋巴瘤-2（Bcl-2）、N-钙黏蛋白和波形蛋白的表达，而上调 Bcl-2 相关 X（Bax）、caspase-3 切割体和 E-钙黏蛋白的表达，而沉默 PCDH8 则观察到对细胞凋亡和凋亡及 EMT 相关蛋白表达的负调控。此外，过表达 PCDH8 显著抑制 AKT 和 GSK3β 的磷酸化，并抑制β-catenin 的表达，而沉默 PCDH8 则产生相反的效果。总之，PCDH8 过表达通过调节 AKT/GSK3β/β-catenin 信号通路抑制结直肠癌细胞的增殖、侵袭、EMT，并诱导细胞凋亡。
