RPF2 and CARM1 cooperate to enhance colorectal cancer metastasis via the AKT/GSK-3β signaling pathway

RPF2 plays a crucial role in promoting epithelial-mesenchymal transition (EMT) and regulating metastasis in colorectal cancer (CRC). By analyzing data from the TCGA and GEO databases, we observed significantly elevated RPF2 expression in CRC, which correlated with EMT markers. Further investigations using stable RPF2 overexpression and knockdown cell lines demonstrated that RPF2 facilitates EMT activation through the AKT/GSK-3β signaling pathway. Notably, CARM1 was identified as a key downstream effector of RPF2. Selective inhibition of CARM1 effectively suppressed the activation of the AKT/GSK-3β pathway and EMT induced by RPF2 overexpression. Both in vitro and in vivo experiments confirmed that RPF2 expression levels positively correlate with the metastatic potential of CRC cells. Moreover, treatment with a CARM1 inhibitor significantly reduced the invasive and migratory capabilities of RPF2-overexpressing cells. These findings suggest that RPF2 drives CRC metastasis by modulating EMT via the AKT/GSK-3β pathway, with CARM1 serving as a critical mediator, offering potential therapeutic targets for CRC.