E-cadherin inhibits the proliferation and migration of human colorectal cancer cells through Hippo signaling pathway

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E-cadherin (E-cad) is a crucial regulatory factor in rescue Epithelial-mesenchymal transition and is involved in the occurrence of various malignant tumor. However, the mechanisms by which E-cadherin regulates tumor metastasis in CRC remain unclear. We established sh-E-cad (silenced by short hairpin RNA) and rescue-E-cad (overexpressed by E-cad plasmid transfection) CRC cell lines to investigate the role of E-cad in CRC in vitro. Immunohistochemistry, clonogenic assays, scratch wound healing assays, CCK-8 assays, flow cytometry, Transwell assay, real time-PCR and Western blot were employed to investigate the underlying mechanisms by which E-cad involve the progression of CRC. In CRC tissues, E-cad expression was significantly reduced, while YAP expression was markedly elevated. Silencing E-cad induced a significant increase of clonogenic ability in CRC cells, which was reduced upon rescue of E-cad expression. Transwell assays indicate that low expression of E-cad enhances the cell migration, a finding corroborated by scratch wound healing experiments. CCK-8 results demonstrate that silencing E-cad promotes the proliferation of CRC cells. Importantly, we found that E-cad influences apoptosis rather than the cell cycle. Analysis of Hippo signaling pathway-related factors revealed that silencing E-cad resulted in significantly decreased expression of MST1/2 and LATS1/2, as well as reduced phosphorylation levels of YAP, while YAP expression was significantly increased. Additionally, immunofluorescence confirmed the nuclear translocation of YAP. Our study indicates that E-cad regulates the malignant progression of CRC via the Hippo signaling pathway, offering a potential new strategy for CRC treatment.
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This study is approved by the Ethics Committee of First Affiliated Hospital of Guangxi University of Chinese MedicineSupporting Agencies
Young Teachers' Research Foundation Improvement Project for Middle-Aged and Young Teachers in Guangxi Colleges and Universities, National Natural Science Foundation of ChinaHow to Cite

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