Colorectal fibroblasts promote malignant phenotype of colorectal cancer cells by activating the ERK signaling pathway
Objective To investigate the effect of human colorectal fibroblast(CCD-18Co)-conditioned medium(CCD18-Co-CM)on biological behaviors of colorectal cancer(CRC)cells and explore the possible molecular mechanisms.Methods Real-time cellular analysis(RTCA),clone formation assay and wound healing assay were used to analyze the changes in proliferation,clone formation,and migration abilities of CRC cell lines HCT116 and Caco-2 treated with CCD18-Co-CM.Western blotting was used to detect the changes in ATK,ERK and STAT3 signaling pathways in the CRC cells activated by CCD18-Co-CM.The effect of CCD18-Co-CM on spheroidization ability of the cells was assessed with sphere-formation assay,and the changes in expressions of CRC stemness markers were detected using RT-PCR.Results CCD-18Co-CM significantly promoted proliferation,colony formation,and migration of HCT116 and Caco-2 cells,enhanced sphere-forming ability and expressions of CRC stemness markers,and increased ERK phosphorylation in the cells.Treatment with SCH772984 effectively inhibited CCD-18Co-CM-induced ERK signaling pathway activation,suppressed the malignant phenotype,and lowered the sphere-forming ability and expression of stemness markers of the two CRC cells.Conclusion Colorectal fibroblasts promote malignant phenotype of CRC cells by activating the ERK signaling pathway.
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