Integrin αVβ3. In non-small-cell lung cancer, OPN promotes inhibitor resistance of acquired epidermal growth factor receptor tyrosine kinase (EGFR-TKI) by upregulating integrin αVβ3 expression and activating downstream FAK/AKT and ERK signaling pathways that promote tumor cell proliferation (17). Here, SPP1 is linked to non-small cell lung carcinoma.