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Cancer‐associated fibroblasts ( CAF s), as the activated fibroblasts in the tumor stroma, are important modifiers of tumour progression. In the present study, we observed that azoxymethane and dextran sodium sulfate treatments induced increasingly severe colorectal mucosal inflammation and the intratumoural accumulation of  CAF s. Fibroblast growth factor ( FGF )‐1 and  FGF ‐3 were detected in infiltrating cells, and  FGFR 4, the specific receptor for  FGF ‐1 and  FGF ‐3, was detected in colon cancer tissues. The phosphorylation of  FGFR 4 enhanced the production of metalloproteinase ( MMP )‐7 and mitogen‐activated protein kinase kinase (Mek)/extracellular signal‐regulated kinase (Erk), which was accompanied by excessive vessel generation and cell proliferation. Moreover, we separated  CAF s, pericarcinoma fibroblasts ( PF s), and normal fibroblasts ( NF s) from human colon tissue specimens to characterize the function of  CAF s. We observed that  CAF s secrete more  FGF ‐1/‐3 than  NF s and  PF s and promote cancer cell growth and angiogenesis through the activation of  FGFR 4, which is followed by the activation of Mek/Erk and the modulation of  MMP ‐7 expression. The administration of  FGF ‐1/‐3‐neutralizing antibodies or the treatment of cells with  FGFR 4 si RNA  or the  FGFR 4 inhibitor  PD 173074 markedly suppressed colon cancer cell proliferation and neovascularization. These observations suggest a crucial role for  CAF s and  FGF  signaling in the initiation and progression of colorectal cancer. The inhibition of the  FGF  signaling pathway may be a useful strategy for the treatment of colon cancer.

FGF ‐1/‐3/ FGFR 4 signaling in cancer‐associated fibroblasts promotes tumor progression in colon cancer through Erk and MMP ‐7