Uev1A promotes breast cancer cell migration by up-regulating CT45A expression via the AKT pathway

Background: UEV1A encodes a ubiquitin-E2 variant closely associated with tumorigenesis and metastasis, but its underlying mechanism in promoting metastasis remains to be investigated. Methods: In this study, we experimentally manipulated UEV1A and CT45A gene expression and monitored their effects on cancer-related gene expression, cell migration and the signal transduction cascade. Results: It was found that UEV1A overexpression induces CT45A family gene expression in breast cancer cells. Indeed, ectopic expression of UEV1A was sufficient to induce CT45A and its downstream genes involved in tumorigenesis, epithelial-mesenchymal transition (EMT), stemness and metastasis, and to promote cell migration and EMT signaling. Consistently, depletion of CT45A abolished the above effects, indicating that CT45A is a critical downstream effector of Uev1A. The Uev1A-induced cell migration and EMT signaling was dependent on AKT but independent of NE-kappa B, indicating that CT45A acts downstream of the AKT pathway. Conclusions: Based on previous reports and observations in this study, we propose that the Ubc13-Uev1A complex activates AKT through K63-linked polyubiquitination, which leads to enhanced CT45A expression, stimulated cell migration and EMT signaling in breast cells. Since similar effects were also observed in a colorectal cancer cell line, the Ubc13/Uev1A-AKT-CT45A axis may also promote tumorigenesis and metastasis in other tissues.

Automated summary

The study demonstrated that overexpression of UEV1A induces the expression of the CT45A family genes, promoting migration and EMT signaling in breast cancer cells. CT45A was identified as a critical downstream effector of Uev1A, and the Uev1A-induced cell migration and EMT signaling primarily depends on the AKT pathway.