癌相关成纤维细胞(CAFs)是肿瘤微环境中重要的间质细胞，其被活化的过程、具体机制及对肿瘤进展的影响尚未完全明确。申请人在前期研究中发现：结直肠癌肿瘤细胞高表达并分泌卵泡抑素样蛋白1（FSTL1）促进肿瘤侵袭转移，且预实验提示微环境中CAFs分布与FSTL1表达具有一致性，rhFSTL1可趋化NFs并诱导其活化为CAFs。因此我们提出结直肠癌细胞分泌的FSTL1能够诱导NFs活化为CAFs，活化的CAFs进一步促进肿瘤进展的研究假说。本课题拟利用Western blot、免疫荧光、免疫共沉淀、质谱分析及GST pull-down、高通量测序与染色质免疫共沉淀等技术阐明FSTL1诱导NFs活化为CAFs的下游信号通路及关键节点；结合体内、体外实验验证结直肠癌细胞通过分泌FSTL1诱导NFs活化为CAFs进而促进肿瘤进展，为以CAFs活化过程为结直肠癌治疗靶点提供理论依据。

Cancer-associated fibroblasts are important mesenchymal cells in tumor microenvironment, but the process and mechanism of their activation and the effect on the tumor progression have not been fully clarified. In the previous study, the applicant found that the colorectal cancer cells over expressed and secreted follistatin like 1 (FSTL1). Our preliminary experiment showed that the distribution of CAFs in colorectal cancer tissues was consistent with the expression level of FSTL1. Additionally, recombinant human cytokine FSTL1 had obvious chemotactic effect on primary normal fibroblasts, and induce them to activate into CAFs. Therefore, we propose the hypothesis that FSTL1 secreted by colorectal cancer cells can induce activation of NFs into CAFs, which further promotes cancer progression. In this study, we will explore the downstream signal pathway and key nodes of FSTL1 regulation of CAFs activation via Western blot, immunofluorescence, immunoprecipitation, GST pull-down, High-throughput sequencing, and then verified through in vivo and in vitro experiments. Our study aims to elucidate the mechanism of colorectal cancer cells to activate CAFs by secreting FSTL1 to promote cancer progression, and to provide a reliable theoretical basis for the activation of CAFs as a therapeutic target for colorectal cancer.