Unraveling the αVβ5-GLUT5 axis in breast cancer: linking extracellular matrix signaling to fructose metabolism: a scoping review.

Breast cancer (BC) is a highly heterogeneous disease marked by diverse molecular subtypes and complex tumor microenvironmental interactions. Recent studies have highlighted the pivotal role of metabolic reprogramming in cancer progression, with fructose metabolism gaining attention as a distinct pathway exploited by tumor cells. Concurrently, the integrin αVβ5 has emerged as a key mediator of extracellular matrix signaling that shapes cancer cell behavior. This review explores the novel and emerging interplay between αVβ5 integrin signaling and the fructose transporter GLUT5 (SLC2A5) in BC pathogenesis. We delineate how αVβ5-mediated ECM signaling modulates the expression and function of GLUT5, facilitating enhanced fructose uptake and utilization to support tumor growth, survival, and metastasis. The review synthesizes evidence from transcriptomic and proteomic datasets, in vitro and in vivo models, and patient-derived data to elucidate the functional crosstalk between these two axes. Additionally, we discuss how this αVβ5–GLUT5 interaction contributes to BC subtype-specific metabolic vulnerabilities and resistance mechanisms. Finally, the therapeutic implications of targeting this axis, including integrin inhibitors and GLUT5-selective blockers, are examined as a framework for metabolic and ECM-directed combinatorial therapies. Understanding the αVβ5–GLUT5 axis offers promising insights into the metabolic-adhesive interface in BC and reveals new opportunities for biomarker development and targeted intervention.