CD151调控整合素α3β1糖基化在乳腺癌侵袭转移中的作用及其机制

乳腺癌死亡的主要原因是复发转移，在肿瘤复发转移中具有重要作用的整合素α3β1既促进也抑制肿瘤发生发展，发生机理不明。我们前期研究发现：α3β1主要调节因子-四跨膜蛋白CD151缺失不引起小鼠乳腺整合素α3β1表达水平改变，但上调了ECM蛋白，并激活了FAK信号。既往研究认为CD151和整合素α3β1形成复合物后，引起整合素α3β1的N-糖基化改变，不同形式N-聚糖具有完全相反的作用。因此，我们推测“CD151和整合素α3β1形成复合物后，导致整合素α3β1发生不同的N-聚糖改变，并影响整合素α3β1下游信号分子及其ECM重塑，从而双向调节肿瘤发生发展”。为此，我们拟采用免疫荧光、CRISPR/Cas9、免疫共沉淀等技术，从临床标本-体外细胞实验-体内动物模型几个层面证实我们的假说，此研究将对阐明整合素α3β1双向调节肿瘤的分子机制有重要意义，并为干预乳腺癌的复发转移提供实验基础和理论依据。

The main cause of breast cancer death is recurrence and metastasis. Integrin α 3 β, which plays an important role in tumor recurrence and metastasis, not only promotes but also inhibits the development of tumor, and the mechanism is unknown. Our previous study showed that the deletion of tetraspanin CD151 which is the main regulatory factor of α 3 β 1, did not change the expression of integrin α 3 β 1 in mammary gland, but up-regulate ECM protein and activate FAK signal. Previous studies suggested that the formation of complex between CD151 and integrin α 3 β 1 resulted in the change of N-glycosylation of integrin α 3 β 1, and different forms of N-glycan had the opposite effect. Therefore, we speculate that "the formation of complex between CD151 and integrin α 3 β 1 leads to the different N-glycan in integrin α 3 β 1 which has influence on downstream signaling molecules of integrin α 3 β 1 and ECM remodeling, and bidirectional regulating tumor tumorigenesis and development". To this end, we are going to confirm our hypothesis from clinical specimens, cell experiments in vitro and animal models in vivo through immunofluorescence, CRISPRR / Cas9, immunocoprecipitation, and so on. This study will not only be of great significance in elucidating the molecular mechanism of integrin α 3 β 1 bidirectional regulating tumor, but also provide experimental and theoretical basis for interfering with the recurrence and metastasis of breast cancer.