Blautia sp.菌/R-spondin3 /β-catenin通路在三阴性乳腺癌进展中的功能及机制研究

已有研究表明菌群失调与三阴性乳腺癌(Triple-negative breast cancer，TNBC)发展密切相关，但调控TNBC发展的具体菌群及其机制目前仍未明了。我们前期研究提示TNBC组织中Blautia sp.量明显上调，且其水平可能与瘤体大小及淋巴结转移相关；体外感染Blautia sp.后TNBC细胞的增殖及迁移能力显著增强；基因芯片结果进一步提示Blautia sp.可能通过活化NF-κB诱导R-spondin3表达，继而激活β-catenin通路促进TNBC进展。本项目拟:（1）在较大样本中进一步明确Blautia sp.分布特征并分析其在TNBC进展中发挥的功能；（2）从体外、体内实验观察Blautia sp./R-spondin3对TNBC细胞恶性生物学行为的影响；（3）深入探讨Blautia sp.发挥功能的相关分子机制。本研究有望为TNBC的治疗提供新思路。

Studies have shown that dysbacteriosis is closely related to the development of triple-negative breast cancer (TNBC), but the related mechanism is still unknown. Our previous study suggested that the expression of Blautia sp. in TNBC tissues was significantly increased, and its level may be correlated to tumor size and lymph node metastasis; In vitro, the proliferation and migration ability of TNBC cells were obviously enhanced after infection with Blautia sp.; and gene chip analysis further indicated that Blautia sp. may induce the R-spondin3 expression through activating NF-κB, and then activate the β-catenin pathway to promote the progress of TNBC. Next, we intends to: (1) further clarify the distribution characteristics of Blautia sp. in a larger samples and analyze its role in TNBC; (2) Observe the Blautia sp. function on TNBC cells in vitro and in vivo experiments, and explore the related molecular mechanism(s). This study is expected to provide new ideas for the treatment of TNBC.