三阴性乳腺癌是乳腺癌中恶性程度较高的一种亚型，其侵袭性强，预后差。FBXW7是一种经典泛素连接酶蛋白，在人类多种恶性肿瘤中发挥抑癌基因作用，但是有关FBXW7在三阴性乳腺癌中的具体作用及相关机制仍不清楚。我们在前期研究中发现FBXW7敲低促进了TNBC干细胞标志蛋白和SOX8的表达，而转录因子YY1敲低导致了FBXW7蛋白上调和SOX8蛋白下调。此外，生物信息预测发现SOX8上有 FBXW7结合的潜在CPD位点，FBXW7启动子区域存在YY1结合的潜在转录调控位点。结合文献推测: FBXW7除通过泛素化降解SOX8蛋白，进而影响与肿瘤干细胞密切相关的Wnt通路外，其还受到上游YY1的转录抑制调控。因此，我们拟以三阴性乳腺癌作为研究对象，通过FBXW7泛素调控机制，深入研究FBXW7调控三阴性乳腺癌肿瘤干细胞的潜在上下游分子机制，为三阴性乳腺癌发生、发展机制及靶向治疗提供理论依据和研究基础。

Triple negative breast cancer (TNBC) is a highly malignant subtype with aggressive characteristic and poor prognosis. FBXW7 is a classic ubiquitin ligase protein that acts as a tumor suppressor gene in a variety of human malignancies, but the specific role and related mechanisms of FBXW7 in TNBC remain unclear. Our preliminary data have shown that knockdown of FBXW7 promoted the expression of TNBC stem cell marker proteins and SOX8, while knockdown of the transcription factor YY1 resulted in upregulation of FBXW7 protein and down regulation of SOX8 protein. Furthermore, bioinformatic analysis predicted that a potential CPD loci for FBXW7 binding in SOX8 and a potential transcriptional regulatory loci for YY1 binding in the FBXW7 promoter region. Combining with the literature, we speculated: FBXW7 not only degrades SOX8 protein through ubiquitination, and then affects the Wnt pathway related to cancer stem cells, but also regulated by upstream YY1 transcriptional repression.Therefore, we plan to conduct an in-depth study of the potential upstream and downstream molecular mechanisms of FBXW7 based on ubiquitylation in TNBC, to further provide theoretical basis for the occurrence, development and targeted therapy of TNBC stem cell .