Proteins in the tripartite motif-containing protein (TRIM) family participates in carcinogenesis. However, little attention was focused on the role of TRIM6 on development of breast cancer. Expression level of TRIM6 was found to be markedly enhanced in breast cancer cells and tissues. Functional assays demonstrated that overexpression of TRIM6 promoted breast cancer progression through increase of YAP1 (Yes-associated Protein 1), while knockdown of TRIM6 suppressed in vitro breast cancer progression and in vivo tumor growth through decrease of YAP1. Co-Immunoprecipitation (co-IP) showed that TRIM6 interacted with STUB1 (stress induced phosphoprotein 1 homology and U-box containing protein 1). TRIM6 promoted ubiquitination-mediated degradation of STUB1 to promote YAP1 signaling. Overexpression of STUB1 attenuated TRIM6-induced promotion of breast cancer growth. In conclusion, TRIM6 contributed to breast cancer progression through ubiquitination-dependent proteasomal degradation of STUB1 and provocation of YAP1 pathway, providing potential therapeutic target for breast cancer.

含三重基序蛋白 (TRIM) 家族中的蛋白质参与癌发生。然而，TRIM6 在乳腺癌发展中的作用却很少受到关注。研究发现乳腺癌细胞和组织中 TRIM6 的表达水平显着增强。功能分析表明，TRIM6 的过度表达通过 YAP1（Yes 相关蛋白 1）的增加促进乳腺癌进展，而 TRIM6 的敲低则通过 YAP1 的减少抑制体外乳腺癌进展和体内肿瘤生长。免疫共沉淀 (co-IP) 显示 TRIM6 与 STUB1（应激诱导的磷蛋白 1 同源性和含有 U-box 的蛋白 1）相互作用。 TRIM6 促进泛素化介导的 STUB1 降解，从而促进 YAP1 信号传导。 STUB1 的过度表达减弱了 TRIM6 诱导的乳腺癌生长促进作用。总之，TRIM6通过泛素化依赖性蛋白酶体降解STUB1和激发YAP1通路促进乳腺癌进展，为乳腺癌提供潜在的治疗靶点。