title: Cell proliferation downregulated by TGF-β2-triggered G1/S checkpoint in clinical CAFs.
abstract: The metabolic reprogramming is indispensible for the fast growth of tumor cells. The metabolism of CAFs is reprogrammed to aerobic glycolysis too. However, it is not clear whether this metabolic reprogramming promotes the growth of CAFs themselves. In this study, we found that the proliferation rate of CAFs was slower than NAFs, which was determined by cell counting, BrdU assay and flow cytometry analysis. Moreover, we found TGF-β signaling regulated cell growth of CAF through RNA-sequencing analysis and Western blot, which was further supported by the observation that TGF-β2 was highly expressed in colon cancer tissues. In the end, we demonstrated that CAFs were critical to tumor cell proliferation, which was supported by the evidence of their close localization in clinical tumor tissue and tumor promoting effect in mice. In brief, our data have manifested that the proliferation rate is decreased in CAFs, which enable CAFs generate more intermediate metabolites to support tumor cells growth, suggesting CAFs is an ideal target for tumor therapy.
authors.affiliation: a Shanghai 9th People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Wu
authors.affiliation: b Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.affiliation: c University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Zongzhi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: d Key laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing , China.
authors.forename: Guochao
authors.initials: G
authors.lastname: Li
authors.affiliation: a Shanghai 9th People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Huang
authors.affiliation: a Shanghai 9th People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xue
authors.affiliation: b Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: d Key laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing , China.
authors.forename: Yingli
authors.initials: Y
authors.lastname: Sun
authors.affiliation: a Shanghai 9th People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Jiangmin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: b Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Jun
authors.initials: J
authors.lastname: Mi
mesh_terms: D000072645:Cancer-Associated Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D049109:Cell Proliferation; D002469:Cell Separation; D003110:Colonic Neoplasms / Q000473:pathology; D015536:Down-Regulation; D059585:G1 Phase Cell Cycle Checkpoints; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D016196:S Phase; D053781:Transforming Growth Factor beta2 / Q000378:metabolism*
chemical_list: D053781:Transforming Growth Factor beta2
keywords: Cancer-associated fibroblasts (CAF); Non-activated fibroblasts (NAF); cell cycle checkpoint; proliferation