HNRNPA2B1 regulates the splicing of MST1R and promotes the expression of a cancer-specific isoform, RON∆165, in head and neck cancer cells. RON∆165 activates the Akt/PKB pathway and leads to increased expression of epithelial to mesenchymal transition regulators such as TWIST2, E-cadherin, vimentin, and ZEB1 and promotes the invasive behavior of head and neck cancer.