Updated project metadata. Aberrant expression of adherens junction (AJ) proteins is frequently observed in human cancers. However, how these factors contribute to tumorigenesis is poorly understood and for some factors such as α‐catenin contradicting data has been described. Systematic analysis of TCGA expression data derived from 23 human tumor types revealed that α‐catenin was significantly reduced in some malignancies (e.g., colon adenocarcinoma), while elevated α‐catenin expression in other entities was associated with poor clinical outcome (e.g., hepatocellular carcinoma; HCC). In HCC cells, α‐catenin was detectable at the membrane as well as cytoplasm where it supported tumor cell proliferation and migration. Additionally, in vivo experiments illustrated moderate oncogenic potential of α‐catenin. To identify functionally relevant binding partners of α‐catenin, BioID combined with mass spectrometry was performed. This led to the identification of cytokinesis regulator centrosomal protein 55 (CEP55) as novel α‐catenin interacting protein in the cytoplasm that was stabilized by α‐catenin. Interestingly, CEP55 was highly expressed in human HCC tissues and its overexpression was transcriptionally controlled by a complex consisting of TEA domain transcription factors (TEADs), forkhead box M1 (FoxM1), and yes-associated protein (YAP). Surprisingly, CEP55 did not significantly affect HCC cell proliferation but supported migration in conjunction with α‐catenin. Together, the enrichment of pro-migratory CEP55 in HCC cells is mediated by two mechanisms: transcriptional activation via the FoxM1/TEAD/YAP as well as the cytoplasmic stabilization through interaction with the AJ protein α‐catenin.