α-catenin interaction with YAP/FoxM1/TEAD-induced CEP55 supports liver cancer cell migration.

Cell–cell contact in epithelial cells is important for cell polarity, cellular compartmentalisation, as well as tissue architecture during development, homeostasis, and regeneration of adult tissues in metazoans. In this context, adherens junctions (AJs) mechanically sense cell contact information with direct impact on cytoskeletal remodelling, the regulation of signalling pathways, and eventually cell biology. Indeed, the loss of cell–cell contact and cellular polarity are key features in human carcinogenesis and important pathological parameters for the identification of many epithelial tumors.We demonstrate in this study, that overexpression of the AJ constituent α‐catenin is frequently observed in human hepatocellular carcinoma (HCC). α‐catenin supports HCC cell proliferation and migration. Together with the oncogene AKT, α‐catenin moderately facilitates tumor initiation in mouse livers. Using mass spectrometry, we identified several new α‐catenin interaction partners in the cytosol of liver cancer cells, including the cytokinesis regulator centrosomal protein 55 (CEP55). CEP55 mediates pro-migratory effects and its overexpression in HCC cells is controlled by two molecular mechanisms: α‐catenin-dependent protein stabilization and transcriptional induction by the TEA domain transcription factors (TEADs)/forkhead box M1 (FoxM1)/yes-associated protein (YAP) complex.In summary, we here describe a new mechanism how changes in cell–cell contact support liver cancer formation and progression. This study demonstrates that dysregulation of the AJ component α‐catenin contributes to liver carcinogenesis via distinct molecular mechanisms. Video Abstract.