USP11调控乳腺发育及肿瘤进程的机制研究

作为去泛素化酶家族成员，USP11通过其作用底物调节细胞功能及肿瘤进程。USP11参与乳腺癌调节虽有报道，但其中的分子机制仍需深入研究。我们的前期结果表明USP11在乳腺上皮细胞分化中发挥重要作用，提示其可能通过调节细胞分化影响乳腺癌细胞功能。为明确USP11在乳腺癌中的作用，本研究将首次利用USP11敲除的乳腺癌模型小鼠，整体观察USP11敲除对乳腺癌发生、发展和转移的影响。此外，我们在人的管腔型乳腺癌细胞中发现了USP11新的互作蛋白E-cadherin。由于E-cadherin在乳腺上皮以及乳腺癌细胞分化功能中发挥关键作用，我们猜测USP11可能通过对E-cadherin去泛素化作用调节乳腺上皮及乳腺癌细胞功能。本课题旨在研究USP11调控乳腺发育和乳腺癌进程的潜在分子机制，为肿瘤诊断、药物开发及个性化诊疗提供新的参考。

As a member of the deubiquitination enzyme family, USP11 is involved in the regulation of cell function and tumor progression through its substrates. The involvement of USP11 in breast cancer regulation has been reported recent years, but the molecular mechanism still needs to be further studied. Our preliminary results indicate that USP11 plays an important role in the differentiation of breast epithelial cells, suggesting that it may influence the function of breast cancer cells by regulating cell differentiation. In order to clarify the role of USP11 in breast cancer, this study will, for the first time, use USP11 knockout breast cancer model mice to investigate the effects of USP11 knockout on the tumor initiation, growth and metastasis. In addition, we identified a novel USP11 interacting protein, E-cadherin, in human luminal breast cancer cells. Since E-cadherin plays an important role in the differentiation of breast epithelium and breast cancer cells, we hypothesize that USP11 regulates breast development and tumor progression through the deubiquitination of E-cadherin. This study aims to investigate the potential molecular mechanism of USP11 in regulating breast epithelial and breast cancer cells function, and to provide a new candidate gene for tumor diagnosis, drug development and personalized diagnosis and treatment.