FNDC4 regulates M2 polarization of tumor-associated macrophages to affect colorectal cancer metastasis.

A very dangerous tumor, colon cancer has the potential to spread and come back. Investigating FNDC4's function in colon cancer and its molecular mechanism is the goal of this study. The expression of FNDC4 and M2 macrophage-related genes (CD163 and CD206) in tumor tissues was found using immunohistochemistry. After transfecting colorectal cancer cells with the FNDC4 knockdown plasmid, CCK8, clone formation, scratch assay, and Transwell test were used to determine cell proliferation, migration, and invasion. Using flow cytometry, the amount of CD163, CD206, and the rate of cell death were found. Western blot was utilized to identify the expression of proteins associated with the Akt/STAT3 pathway, M2 macrophages, and epithelial-mesenchymal cells. To see how sh-FNDC4 affected tumor growth, a xenograft tumor model was created, and H&E staining was used to look at liver tissue metastases. The findings demonstrated that FNDC4 was favorably connected with the expression of CD206 and CD163 and that it was substantially expressed in colorectal cancer. Tumor cell proliferation, migration, invasion, EMT, and M2 macrophage polarization were all reduced by FNDC4 knockdown. Furthermore, FNDC4 knockdown suppressed tumor growth and liver metastasis in vivo by blocking the Akt/STAT3 pathway. In conclusion, FNDC4's modulation of the Akt/STAT3 pathway may be the reason why its knockdown prevented colorectal cancer cell proliferation, metastasis, and M2 macrophage polarization.