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

α-连环蛋白在组织完整性、修复和胚胎发育中发挥着关键作用。然而，α-连环蛋白的翻译后修饰及其在调节癌症进展中的相关作用仍不清楚。在这里，我们报告 α-连环蛋白被 p300 乙酰化，并确定了三个乙酰化位点：K45、K866 和 K881。相反，α-连环蛋白乙酰化可以被脱乙酰酶 HDAC6 逆转。从机制上讲，α-catenin 乙酰化通过阻断 α-catenin 与 Yap1 之间的相互作用，释放转录共激活因子 Yes 相关蛋白 1 (Yap1)，并促进 Yap1 在细胞核中的积累。通过这种机制，乙酰化削弱了α-连环蛋白抑制小鼠乳腺癌细胞增殖和肿瘤生长的能力。同时，我们发现CDDP诱导α-catenin乙酰化，乙酰化的α-catenin在CDDP条件下抵抗细胞凋亡。此外，乙酰化可抑制 α-catenin 的蛋白酶体依赖性降解，从而增强 α-catenin 的储存稳定性。总而言之，我们的结果表明 α-连环蛋白可以被乙酰化，这一事件对于 Yap1 的亚细胞分布和随后促进乳腺肿瘤发生至关重要。