Pyridoxal kinase (PDXK) facilitates CRC progression by releasing beta-catenin from the GSK-3β destruction complex

Abstract

Abstract Studies have suggested a close association between hyperactivation of the catenin beta 1 gene (CTNNB1) and the occurrence and progression of colorectal cancer (CRC). Here, we report that Pyridoxal kinase (PDXK) promotes the development of colorectal cancer through Wnt signaling pathway. The expression of PDXK is elevated in CRC patients and is associated with an unfavourable prognosis. Genetic depletion of PDXK significantly inhibited CRC cell viability, viability, and migration both in vitro and in vivo. Furthermore, we observed that overexpression of PDXK enhanced CRC cell viability, invasion, and migration, and these effects were dependent on its kinase activity. GSEA revealed a strong association between PDXK expression and the Wnt signaling pathway, which was validated through luciferase reporter assays and RT-qPCR. Mechanistically, PDXK was found to activate the Wnt signaling pathway by interacting with GSK-3β and releasing beta-catenin from the GSK-3β destruction complex, thereby promoting tumorigenesis. These findings provide direct insights into the molecular mechanisms underlying the functions of PDXK in CRC and suggest it as a potential therapeutic target for combating colorectal cancer.