Crosstalk between integrin signaling and NAD⁺ biosynthetic pathways promotes glycolysis, proliferation, survival, and tumor growth in triple-negative breast cancer.

pathways converged on Wnt/β-catenin signaling to regulate DNA repair, and response to PARP1/2 inhibitors. Co-inhibiting FAK and NAMPT synergistically suppressed tumor growth by approximately 80%. Elevated stromal NAMPT expression was associated with a trend toward favorable clinical outcomes. Collectively, these findings uncover a previously unrecognized crosstalk between integrin/FAK and NAMPT/NAD⁺ pathways in TNBC and identify a synthetic lethal-like therapeutic vulnerability that warrants further evaluation in clinically relevant models.