LRRC56调控RhoA/ROCKs信号通路影响细胞骨架促进乳腺癌转移的机制研究

乳腺癌转移是导致乳腺癌患者死亡的重要原因。抑制细胞骨架形成能够有效治疗转移性乳腺癌。RhoA/ROCKs信号通路对于细胞骨架形成具有重要的调控作用。前期研究提示抑制RhoA/ROCKs信号通路，可提高乳腺癌肺转移动物模型的生存周期。LRRC56在转移性乳腺癌中显著高表达；改变乳腺癌细胞中LRRC56表达之后，RhoA/ROCKs信号通路随之改变，乳腺癌细胞的增殖、运动能力受到显著影响；细胞骨架形成随之改变。预实验表明LRRC56可与IFT88相互作用介导，可能通过YAP1影响ECM调控RhoA/ROCKs信号通路，但具体机制仍不明确。.本课题拟验证LRRC56在乳腺癌中的生物学功能及对乳腺癌转移的作用；采用蛋白质谱与免疫共沉淀技术，寻找并验证与LRRC56互作蛋白，并探究LRRC56介导YAP1影响ECM调控RhoA/ROCKs的具体作用机制，从而为临床转移性乳腺癌的治疗提供新的治疗靶点。

Cancer metastasis is an important cause of death to breast cancer. Inhibition of cytoskeleton formation can effectively treat metastatic breast cancer. The RhoA/ROCKs signaling pathway plays an important role in regulating the formation of cytoskeleton. Previous studies have suggested that inhibiting the RhoA/ROCKs signaling pathway can improve the survival cycle of animal models of breast cancer lung metastasis. LRRC56 is significantly highly expressed in metastatic breast cancer; after changing the expression of LRRC56 in breast cancer cells, the RhoA/ROCKs signaling pathway changes accordingly, and the proliferation and motility ability of breast cancer cells are significantly affected; cytoskeleton formation is also affected accordingly. Mechanism experiments show that LRRC56 can interact with IFT88 and mediate YAP1 to influence ECM to regulate RhoA/ROCKs signaling pathway, but the specific mechanism is still unclear...This project intends to verify the biological function of LRRC56 in breast cancer and its effect on breast cancer metastasis; using protein profiling and immunoprecipitation technology to find and verify the interaction protein with LRRC56, and to explore the influence on YAP1, which mediated by LRRC56 on ECM regulation to RhoA/ ROCKs signal pathway. This could provide a novel possible targeted treatment to metastatic breast cancer.