TRIM24 promotes colorectal cancer cell progression via the Wnt/β-catenin signaling pathway activation.

Overexpression of TRIM24 is observed in several human cancers and is correlated with an increase in the progression and metastasis of tumors. In this study, we investigated the changes in activity and biochemical events that occur after overexpression of TRIM24 in a colorectal cancer (CRC) mouse model. We observed upregulated TRIM24 expression in CRC tissues compared to that in nonneoplastic adjacent tissues. Enhanced expression of TRIM24 was significantly associated with the status of lymph nodes and poor recurrence-free survival of patients with CRC. The role of TRIM24 in CRC tumor growth was investigated using an orthotopic model of MC38 mouse colon cancer cells overexpressing TRIM24, and CRC tumor growth was found to increase dramatically by TRIM24 overexpression. Moreover, angiogenesis was stimulated by TRIM24 overexpression via the upregulation of vascular endothelial growth factor (VEGF) expression. Overexpression of TRIM24 in MC38 cells led to an increase in the protein levels of ALDH1 and other stem cell markers. In addition, we observed that Wnt/β-catenin signaling is required for the function of TRIM24 in CRC cells. Tumor-associated macrophages (TAMs) were found to be recruited by tumor cells overexpressing TRIM24 via the increased expression of CCL2/5, CSF-1, and VEGF, further enhancing CRC tumor growth. In conclusion, overexpression of TRIM24 facilitates the growth of CRC and the remodeling of the tumor stroma via angiogenesis stimulation and TAM recruitment. The Wnt/β-catenin pathway is a possible crucial link in the TRIM24-associated progression of tumors, which may provide opportunities for pharmacological intervention.