a-Catenin acetylation is essential for its stability and blocks its tumor suppressor effects in breast cancer through Yap1

& alpha;-Catenin plays a critical role in tissue integrity, repair, and embryonic development. However, the post-translational modifications of & alpha;-catenin and the correlative roles in regulating cancer progression remain unclear. Here, we report that & alpha;-catenin is acetylated by p300, and identify three acetylation sites, K45, K866, and K881. Conversely, & alpha;-catenin acetylation can be reversed by deacetylase HDAC6. Mechanistically, & alpha;-catenin acetylation releases the transcriptional coactivator Yes-associated protein 1 (Yap1) by blocking the interaction between & alpha;-catenin and Yap1, and promotes the accumulation of Yap1 in the nucleus. Through this mechanism, acetylation weakens the capacity of & alpha;-catenin to inhibit breast cancer cell proliferation and tumor growth in mice. Meanwhile, we show that CDDP induces acetylation of & alpha;-catenin, and acetylated & alpha;-catenin resists the apoptosis under CDDP conditions. Additionally, acetylation inhibits the proteasome-dependent degradation of & alpha;-catenin, thus enhancing the stability of & alpha;-catenin for storage. Taken together, our results demonstrate that & alpha;-catenin can be acetylated, an event that is key for the subcellular distribution of Yap1 and subsequent facilitation of breast tumorigenesis.