Single-cell analysis reveals that cancer-associated fibroblasts stimulate oral squamous cell carcinoma invasion via the TGF-β/Smad pathway  

作　　者：Wenbin Yang Shunhao Zhang Tianle Li Zirui Zhou Jian Pan 

机构地区：[1]State Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,Department of Oral and Maxillofacial Surgery,Department of Medical Affairs,West China Hospital of Stomatology,Sichuan University,Chengdu 610041,China [2]State Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu 610041,China [3]Faculty of Dentistry,University of Hong Kong,Prince Philip Dental Hospital,HKSAR,China [4]State Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,Department of Oral and Maxillofacial Surgery,West China Hospital of Stomatology,Sichuan University,Chengdu 610041,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第2期262-273,共12页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the Research and Develop Program,West China Hospital of Stomatology Sichuan University(No.LCYJ2019-1 to J.P.);the Interdisciplinary and Intercollege Research Project of the State Key Laboratory of Sichuan University(No.2021KXK0403 to J.P.);the Sichuan University-Panzhihua City 2021 Campus Cooperation Special Fund Project(No.2021CDPZH-7 to W.Y.);the College Students’Innovative Entrepreneurial Training Plan Program(No.202210610194 to S.Z.).

摘　　要：Although substantial progress has been made in cancer biology and treatment,the prognosis of oral squamous cell carcinoma(OSCC)is still not satisfactory because of local tumor invasion and frequent lymph node metastasis.The tumor microenvironment(TME)is a potential target in which cancer-associated fibroblasts(CAFs)are of great significance due to their interactions with cancer cells.However,the exact mechanism is still unclear.Therefore,we focus on the crosstalk between cancer cells and CAFs and discover that CAFs are the main source of TGF-β1.Transwell assays and western blot analysis further prove that CAFs activate the TGF-β1/Smad pathway to promote OSCC invasion.Through survival analysis,we confirm that CAF overexpression is correlated with poor overall survival in OSCC.To further elucidate the origin and role of CAFs in OSCC,we analyze single-cell RNA sequencing(scRNA-seq)data from 14 OSCC tumor samples and identify four distinct cell types,including CAFs,in the TME,indicating high intratumoral heterogeneity.Then,two subtypes of CAFs,namely,myofibroblasts(mCAFs)and inflammatory CAFs(iCAFs),are further distinguished.Based on the differentially upregulated genes of mCAFs and iCAFs,GO enrichment analysis reveals their different roles in OSCC progression.Furthermore,the gene expression pattern is dynamically altered across pseudotime,potentially taking part in the transformation from epithelial to mCAFs or iCAFs through the epithelial to mesenchymal transition.

关 键 词：oral squamous cell carcinoma cancer-associated fibroblast MYOFIBROBLAST TGF-Β single cell 

分 类 号：R739.8[医药卫生—肿瘤]