STK25 Inhibits Epithelial-Mesenchymal Transition and Metastasis via the TGF-β/SMAD2 Signaling Pathway in Colorectal Cancer.

The metastatic potential of colorectal cancer (CRC) is a pivotal determinant of patient prognosis. Serine/threonine protein kinase 25 (STK25) is critically involved in diverse biological processes, and the function of STK25 in tumorigenesis and metastasis remains debatable across distinct tumor types. Here we identified that low STK25 expression was associated with increased tumor metastasis and poor survival in CRC patients. Functional experiments revealed that STK25 knockdown promoted CRC cells' epithelial-mesenchymal transition (EMT) and metastasis in vitro and in vivo. Mechanistically, STK25 depletion promoted migration and EMT progression through the TGF-β signaling pathway, and the kinase activity of STK25 was required to inhibit TGF-β signaling activation. These findings establish STK25 as a promising therapeutic target for intervening in TGF-β/SMAD2-mediated metastasis in CRC.