乳腺癌是女性最常见的恶性肿瘤，三阴性乳腺癌（约占15-20%）恶性程度高且缺乏有效治疗靶点，是目前乳腺癌治疗难点。已知脂代谢调控和肿瘤干细胞的自我更新在肿瘤的发生发展中有重要作用。我们前期工作初步发现，炎症因子TNFα诱导KLF5和AP1（c-Jun/Fra-1）转录因子可能协同促进脂肪酸从头合成和三阴性乳腺干细胞的自我更新，本研究拟进一步明确转录因子KLF5和AP1是否在炎症条件下协同促进脂肪酸合成从而促进三阴性乳腺癌干细胞，解析炎症条件下转录因子KLF5和AP1形成转录复合物并协同调节下游基因转录的分子机制，明确其临床意义，探讨能否通过靶向KLF5和AP1互作及脂代谢从头合成相关酶进而抑制三阴性乳腺癌干细胞。本研究旨在明确KLF5与AP1在脂肪酸从头合成途径和三阴性乳腺癌干细胞自我更新方面的功能及分子机制，从而为三阴性乳腺癌的治疗提供有效线索。

Breast cancer is the most frequent cancer among women. Triple-negative breast cancer (TNBC) accounts for about 15-20% of all breast cancers, and tends to be a more aggressive subtype of breast cancer. TNBC can be very difficult to deal with, especially because there aren't targeted therapies available. It is well known that lipid metabolism and self-renewal of tumor stem cells play important roles in tumorigenesis. In our previous work, we found that transcription factors KLF5 and AP1 (c-Jun/Fra-1) can synergistically promote de novo fatty acid synthesis and self-renewal of triple-negative stem cells. In this study we will first determine whether KLF5 and AP1 indeed promote fatty acid synthesis and BCSC in response to inflammation. Then, we will figure out the assembly process of KLF5 and AP1 transcription factor complex under inflammatory. After that we plan to characterize the function of downstream target genes co-regulated by KLF5 and AP1. Consequently, we will test whether the expression level of KLF5/AP1 and their target genes are associated with prognosis. Finally, we will explore the strategies to suppress the proliferation and metastasis of TNBC by inhibitors of KLF5, AP1 and fatty acid synthesis-related enzymes. Therefore, the aim of this project is to determine the function and mechanism of KLF5 and AP1 in de novo fatty acid synthesis and self-renewal of triple-negative breast stem cells and to develop new therapeutics for TNBC.