Crosstalk between insulin-like growth factor (IGF) receptor and integrins through direct integrin binding to IGF1

•IGF1 directly binds to integrins and induces ternary complex formation (integrin, IGF1, and IGF1R) on the cell surface. The integrin-binding defective IGF1 mutant is defective in inducing IGF signaling, although the mutant still binds to IGF1R.•The integrin-binding defective IGF1 mutant is dominant-negative and suppresses cell proliferation induced by wt IGF1, and suppresses tumorigenesis in vivo.•IGF1 signaling is detected in anchorage-independent conditions (in the absence of integrin-ECM interaction), suggesting that integrin-IGF1 interaction, rather than integrin-ECM interaction, is important for IGF signaling.•In addition to IGF1, several other cytokines (FGF, neuregulin-1, fractalkine) directly bind to integrins and induce ternary complex formation, suggesting that integrins act as co-receptors common to these cytokines.