我国是食管鳞状细胞癌（ESCC）的高发国家之一。由于肿瘤的异质性，单纯在肿瘤细胞中进行研究有局限性。因此，亟待深入的研究肿瘤细胞和肿瘤相关成纤维细胞（CAFs）的相互作用。前期研究发现，CAFs可以增加肿瘤细胞的增殖，降低Hedgehog（Hh）通路抑制剂对肿瘤细胞增殖的抑制；NIH/3T3 Smo KD稳定敲减细胞上清对肿瘤细胞的增殖支持减弱；蛋白质组学方法发现NIH/3T3 Smo KD细胞上清液中细胞外基质蛋白Col4a2、Col6a1、Col6a2和Thbs4显著下降，且均参与PI3K-AKT通路。在此基础上提出科学假说：CAFs通过Hh-PI3K-AKT通路支持ESCC细胞的增殖。为验证假说，首先阐明CAFs对肿瘤细胞的增殖支持作用是否来源于Hh-PI3K-AKT通路及其作用机理；然后，在裸鼠模型和人ESCC组织中将体外研究结果进行验证。本项目将增加CAFs对ESCC作用的认识。

China has high incidence of esophageal squamous cell carcinoma (ESCC). Due to the heterogeneity of cancers, studies in cancer cells alone have limitations. Therefore, it is urgent to study the interaction between cancer cells and cancer-associated fibroblasts (CAFs). Previous studies have found that CAFs can increase the proliferation of ESCC cells and reduce the inhibition of proliferation on cancer cells by the Hedgehog (Hh) pathway inhibitors. We established a stable Smoothened (SMO) knocking down NIH/3T3 cell line, NIH/3T3 Smo KD. The conditional medium collected from NIH/3T3 Smo KD cells had less proliferation support to ESCC cells. Proteomics method showed that the extracellular matrix proteins Col4a2, Col6a1, Col6a2 and Thbs4 in conditional medium of NIH/3T3 Smo KD cells were significantly decreased, and all involved in the PI3K-AKT pathway. Based on our results, this project proposes the scientific hypothesis that CAFs support the proliferation of ESCC cells through the Hh-PI3K-AKT pathway. To verify the hypothesis, we elucidated whether CAFs support the proliferation of ESCC cells through the Hh-PI3K-AKT pathway and its mechanism in vitro. These results were further verified in the nude mice model and human ESCC tissues. This project increases our understanding of the role of CAFs in ESCC.