目前认为癌相关成纤维细胞（CAFs）的不同转化状态关系着恶性肿瘤发生发展进程。申请者近期发现口腔CAFs上皮样转化的新现象，并证实口腔CAFs呈现活跃的糖代谢重编程；因癌上皮细胞的转化受糖代谢诱导，藉此，申请者提出“糖代谢重编程可能是口腔CAFs上皮样转化的重要驱动机制”新假说。本项目拟联合采用免疫细胞化学、流式分选、全基因表达谱、基因转染、蛋白质组学、3D细胞球、复合移植瘤模型及系统生物学等技术，研究①口腔CAFs被诱导发生上皮化的特征及影响因素；②此类上皮样细胞是否对口腔癌细胞株和癌干细胞的生物学特性产生影响；③糖代谢重编程及其关键调控酶M2型丙酮酸激酶（PKM2）对CAFs上皮化过程是否具有驱动作用及其分子调控机制；④靶向干预PKM2是否对口腔鳞癌产生阻抑效应。本项目对了解口腔CAFs新转化现象的作用及其驱动机制，制订有效抑癌新策略具有重要的理论意义和应用价值。

At present, it’s recognized that the different transformation status of carcinoma-associated fibroblasts (CAFs) is closely related to the development of malignant tumors. For the first time, the applicant recently discovered a new phenomenon that oral CAFs can undergo epithelial-like transition, and verified oral CAFs showed active glucose metabolism reprogramming. Cause the transformation of cancer cells is drived by glucose metabolism. Therefore, the applicant first proposed the new hypothesis that “glucose metabolism reprogramming may also be the essential driving force for oral CAFs’ epithelial-like transition. The project will apply immunocytochemistry, flow cell sorting, global gene expression profiling, gene transfection, proteomics, 3D cell sphere forming, tumor transplant model and system biology to explore: ①The characters and influence factors of oral CAFs’ induced epithelial-like cells; ②Whether such epithelial-like cells can influence the biological characters of oral cancer cell lines and oral cancer stem cells; ③ Whether the epithelial-like transition of oral CAFs can be drived by glucose metabolism reprogramming and its key enzyme M2 pyruvate kinase(PKM2). If it’s yes, then what’s the molecular driving mechanism; ④Whether the targeted intervention of PKM2 can impede the development of oral squamous cell carcinoma. This project possesses important theoretical and application value to understand the role and driving mechanism of oral CAFs’ new transformation phenomenon, thus help discover effective strategies for tumor-supressing.