Galectin-3 binding protein promotes cell motility in colon cancer by stimulating the shedding of protein tyrosine phosphatase kappa by proprotein convertase 5

► The ectodomain of PTPκ is cleaved by a processed form of proprotein convertase 5 (PC5A) in WiDr colon cancer cells. ► Galectin-3 binding protein facilitates PTPκ shedding by decreasing the availability of cell surface-bound galectin-3. ► Galectin-3 binding protein promotes cancer cell migration by activating the PTPk shedding. ► The ratio of galectin-3 binding protein to galectin-3 can be a molecular indicator for colon cancer progression. It has previously been reported that shedding of the PTPκ ectodomain drives enhanced motility of colon cancer cells. Herein, we provide mechanism underlying the regulation of PTPκ shedding by galectin-3 binding protein. PTPκ was inarguably scissored by the processed form of proprotein convertase 5 (subtilisin/kexin type 5), and galectin-3 binding protein which is over-produced in colon cancer cells and tissues contributed to increased cancer cell motility by acting as a negative regulator of galectin-3 at the cell surface. The high expression ratio of galectin-3 binding protein to galectin-3 was clinically correlated to lymphatic invasion. These results suggest that galectin-3 binding protein may be a potential therapeutic target for treatment of, at least, colon cancer patients with high expression of galectin-3 binding protein.