乳腺癌是女性最常见的恶性肿瘤，调控其进展的机制还未完全阐明。癌间质微环境，尤其是癌相关成纤维细胞(CAFs)，在癌症进展中发挥关键的作用，而CAFs在乳腺癌进展中的功能和机制还未详细阐述。我们的研究结果表明CAFs促进乳腺癌的生长迁移和侵袭，高通量测序分析显示转录因子ETS1在CAFs中高表达并参与了近半数显著上调基因的转录调控。CAFs中敲低ETS1可抑制其促乳腺癌迁移和侵袭能力。HTRI数据与预实验显示CAFs中敲低ETS1抑制了白血病抑制因子(LIF)的转录，提示LIF可能是ETS1下游靶点。因此，我们提出科学假设：乳腺癌CAFs中ETS1高表达，导致LIF合成和分泌增加，从而促进乳腺癌进展。本项目拟从细胞和动物两层面阐释CAFs在乳腺癌进展中的功能，探究ETS1在乳腺癌CAFs中的作用，并深入研究CAFs中ETS1/LIF信号促乳腺癌进展的机制，为乳腺癌的治疗提供新的理论依据。

Breast cancer is now the most common malignant tumor in women. The mechanisms underlying breast cancer progression have not been fully elucidated. Cancer microenvironment, especially cancer associated fibroblasts(CAFs), has been proved to be essential for cancer progression. However, the role of CAFs in breast cancer progression has not been well defined. Our primary experiments demonstrate that CAFs can promote the growth, migration and invasion of breast cancer. The high-throughput sequencing data display that ETS1 is highly expressed and involved in the transcriptional regulation of nearly half of significantly upregulated genes in CAFs. Knockdown of ETS1 in CAFs attenuates the pro-invasive and pro-migratory effects of CAFs on breast cancer cells. Moreover, HTRI data analyses and the results that knockdown of ETS1 in CAFs leads to decreased leukemia inhibitory factor(LIF) mRNA levels, indicate that LIF is probably the downstream target of ETS1 in CAFs. Thus, we propose the hypothesis that highly expressed ETS1 in CAFs increases the production and secretion of LIF, which promotes the progression of breast cancer. Based on in vitro and in vivo experiments, our project aims to elucidate the function of CAFs during the progression of breast cancer, to explore the role of ETS1 in CAFs and further study the mechanisms of ETS1/LIF signaling in CAFs, which will provide a new theoretical basis for the treatment of breast cancer.