Osteopontin‐integrin αvβ3 axis is crucial for 5‐fluorouracil resistance in oral squamous cell carcinoma

Clinical applications of a chemotherapeutic agent, 5‐fluorouracil (5‐FU) in oral squamous cell carcinoma (OSCC) have been limited because of drug resistance. This study aimed to identify novel mechanisms of 5‐FU resistance. Here we found increased osteopontin (OPN) gene expression in OSCC tissues with resistance to 5‐FU‐based chemoradiotherapy. OPN overexpression in OSCC cells led to 5‐FU resistance and abrogated the prosurvival effect of the drug in a mouse xenograft model. OPN‐induced 5‐FU resistance required integrin α v β 3 . Targeting integrin α v β 3 reversed the resistance in a 5‐FU‐resistant clone highly expressing OPN. Our data suggest that the OPN‐integrin α v β 3 axis is crucial for 5‐FU resistance in OSCC.