Colorectal fibroblasts promote malignant phenotype of colorectal cancer cells by activating the ERK signaling pathway
Objective: To examine the impact of conditioned medium from human colorectal fibroblasts (CCD-18Co-CM) on the biological behaviors of colorectal cancer (CRC) cells and to investigate the underlying molecular mechanisms.
Methods: Changes in the proliferation, colony formation, and migration of CRC cell lines (HCT116 and Caco-2) treated with CCD-18Co-CM were analyzed using real-time cellular analysis (RTCA), colony formation assay, and wound healing assay. Western blotting was performed to evaluate alterations in the activation of the AKT, ERK, and STAT3 signaling pathways. Sphere-formation assays were conducted to assess the spheroidization capacity of CRC cells, while RT-PCR was used to measure the expression of CRC stemness markers.
Results: Treatment with CCD-18Co-CM significantly enhanced the proliferation, colony formation, migration, and sphere-forming ability of HCT116 and Caco-2 cells. It also upregulated the expression of CRC stemness markers and increased ERK phosphorylation. The ERK pathway inhibitor SCH772984 effectively suppressed CCD-18Co-CM-induced ERK activation, reducing the malignant phenotype, sphere-forming ability, and stemness marker expression in both CRC cell lines.
Conclusion: Colorectal fibroblasts promote the malignant phenotype of CRC cells by activating the ERK signaling pathway.