在乳腺癌的微环境中，含有丰富的癌相关成纤维细胞（CAF）和细胞外ATP。我们研究团队在国际上首次提出肿瘤微环境中的ATP是重要的促侵袭因子。然而，细胞外ATP促肿瘤侵袭机制并不很清楚，肿瘤细胞如何“驯化”成纤维细胞为CAF的机制更是所知甚少。本课题组的预实验结果显示：细胞外ATP可以通过SOX9及其下游分子S100A4等促进乳腺癌细胞侵袭，并且激活成纤维细胞；在Balb/c裸鼠成瘤模型中，腹腔内注射ATP水解酶Apyrase及注射特异性S100A4转录抑制剂Niclosamide，可以明显抑制肿瘤的肺转移以及移植瘤间质的CAF活性。本项目旨在阐明细胞外ATP通过SOX9促进乳腺癌细胞侵袭、并协同肿瘤细胞激活成纤维细胞的分子机制，为乳腺癌的治疗提供新思路及分子靶点。以SOX9或其下游关键分子为靶点，有可能在杀伤肿瘤细胞的同时，破坏肿瘤生长的沃土（即CAF），一箭双雕，达到更好的治疗效果。

The breast cancer microenvironment contains not only tumor cells, but also abundant cancer-associated fibroblasts (CAFs) and extracellular ATP. Our team first reported that ATP is an important pro-invasion factor in the tumor microenvironment. However, a more comprehensive mechanism of ATP-induced invasiveness is not clear, and how tumor cells managed to "domesticate" fibroblasts into CAFs remains poorly understood. Our previous work has demonstrated that apart from stimulating breast cancer cell motility via SOX9 downstream effector S100A4, ATP assisted breast cancer cells in transforming fibroblasts into cancer-associated fibroblast (CAF)-like cells. Both apyrase and niclosamide treatments could inhibit lung metastasis of inoculated tumors in Balb/c mice model, and CAFs from these treated tumors exhibited weakened migration-stimulating capacity. This research aims to elucidate the molecular mechanisms through which ATP promotes breast cancer cell invasion via SOX9 and works synergistically with tumor cells to transform fibroblasts into CAFs，providing new pre-clinical ideas and therapeutic targets for breast cancer intervention, hoping to not only kill off tumor cells, but destroy the environment they thrive in (CAFs) as well.