CAFs源性POSTN介导GLI2-CD147正反馈环路促进口腔鳞癌进展的机制研究

口腔鳞癌具有高度侵袭性，其恶性进展有赖于肿瘤微环境中肿瘤相关成纤维细胞(CAFs)与邻近肿瘤细胞相互作用，但其作用机制尚不明确。申请人前期发现，CAFs源性periostin（POSTN）促进口腔鳞癌生长；POSTN和CD147增加肿瘤细胞GLI2核蛋白表达，而GLI2可转录上调CD147表达。据此提出科学假说：CAFs源性POSTN通过调控GLI2-CD147正反馈环路持续转录激活CD147基因表达，促进口腔鳞癌恶性进展。本课题将从组织、细胞、分子和动物层面观察和分析：CAFs源性POSTN上调CD147表达促进口腔鳞癌生长的作用；POSTN通过GLI2-CD147正反馈环路持续上调CD147表达的分子机制；并通过口腔鳞癌标本和荷瘤鼠模型分析验证POSTN和CD147靶点在口腔鳞癌诊治中的潜在价值。研究为揭示口腔鳞癌发生发展机制提供新视角，为靶向干预该信号轴遏制肿瘤恶性进展提供科学依据。

Oral squamous cell carcinoma (OSCC) is highly aggressive. The progression of OSCC depends on the interaction of cancer cells and cancer associated fibroblasts (CAFs) in the tumor microenvironment. We have demonstrated that CAFs-derived periostin (POSTN) promoted the tumor growth in OSCC, POSTN and CD147 increased the expression of GLI2 in the nucleus, and GLI2 could transcriptionally increase the expression of CD147. Therefore, we hypothesized that CAFs-derived POSTN enhanced the expression of CD147 through GLI2-CD147 positive loop, to promote the progression of OSCC. This study aimed to investigate the function of CAFs-derived POSTN in promoting the expression of CD147 and tumor growth in OSCC, how POSTN enhanced the expression of CD147 through the GLI2-CD147 positive loop, and further confirmed the potential role of POSTN and CD147 in the diagnosis and treatment of OSCC through using OSCC samples and the xenograft models. This study will provide new perspective for revealing the mechanism of malignant behavior, and provide theoretical basis for targeting the signal to inhibit tumor progression in OSCC.