Silencing CXCR6 promotes epithelial-mesenchymal transition and invasion in colorectal cancer by activating the VEGFA/PI3K/AKT/mTOR pathway.

This study investigated the role of C-X-C motif chemokine receptor 6 (CXCR6) in colorectal cancer (CRC). It was found that lower CXCR6 expression is correlates with poorer prognostic outcomes, suggesting that CXCR6 may inhibit tumor progression and thus improve patient outcomes. Silencing CXCR6 in CRC cell lines SW620 and CT-26 resulted in significantly enhanced migration and invasion, as demonstrated by wound healing and transwell assays. Further analysis revealed that CXCR6 activity is associated with activation of the VEGFA/PI3K/AKT/mTOR signaling pathway. Inhibition of this pathway through VEGFA siRNA and pathway-specific inhibitors reversed the effects of CXCR6 silencing on cell migration and invasion. Moreover, xenograft experiments showed that silencing CXCR6 led to increased tumor growth and upregulated proteins associated with the extracellular matrix and epithelial-mesenchymal transition. These findings were validated through immunohistochemical, immunofluorescence, and Western blot analyses. This study highlights CXCR6's critical role in CRC and its potential as a therapeutic target to manage cancer progression.