三阴性乳腺癌（TNBC）微环境中癌相关脂肪细胞（CAA）在肿瘤转移中起关键作用，但CAA重编程及其促TNBC转移的机制尚未完全阐明。本项目预初实验发现糖代谢压力信号琥珀酸/GPR91在TNBC的CAA中显著高于其它乳腺癌亚型，且与肿瘤转移密切相关；深入研究发现抑制脂肪细胞GPR91信号，其促TNBC转移以及重编程CAA、分泌透明质酸和活化分子伴侣介导的自噬（CMA）作用均被显著抑制；初步发现GPR91受肿瘤细胞外泌体来源miR-122-5p上游调控。因此，本项目聚焦的科学问题是：琥珀酸/GPR91信号诱导CAA重编程促进TNBC转移的机制。项目将从TNBC脂肪和代谢压力微环境切入，阐明TNBC转移中琥珀酸/GPR91信号诱导CAA重编程和分泌透明质酸的作用机制，解析CMA参与的关键调控网络及肿瘤细胞外泌体来源miRNA上调GPR91表达的分子机制，为干预肿瘤微环境治疗TNBC提供新靶点。

Cancer associated adipocyte (CAA) plays a key role in cancer metastasis in the adipose microenvironment of triple negative breast cancer (TNBC), but the mechanism of reprogramming CAA and promoting cancer metastasis is still unclear. In the preliminary experiments of this project, it was found that succinic acid/GPR91 was significantly higher in TNBC CAA than non-TNBC, and was closely related to clinical metastasis; GPR91 knockdown in adipocytes inhibited the functions of promoting TNBC metastasis, reprogramming CAA, secreting hyaluronic acid and activating molecular chaperone-mediated autophagy (CMA); GPR91 was regulated by miR-122-5p. Therefore, the scientific question of this project is that succinic acid/GPR91 signal induces CAA reprogramming and its mechanism of promoting TNBC metastasis. The project focuses on the microenvironment of TNBC fat and metabolic pressure, studies the role of succinic acid/GPR91 signal inducing CAA reprogramming and secreting hyaluronic acid in promoting tumor metastasis, analyzes the key mechanism of CMA and the effect of exosomal miR-122-5p from TNBC cells on regulating GPR91 expression, which provides a new target for TNBC microenvironment.