ITGB4

Integrin beta-4 (ITGB4), also known as CD104, is a transmembrane receptor subunit that pairs with integrin alpha-6 to form the α6β4 heterodimer. This laminin-binding integrin is prominently expressed in epithelial cells, anchoring hemidesmosomes to the basement membrane and regulating cell-matrix adhesion. Its uniquely long cytoplasmic domain facilitates interactions with signaling adaptors like plectin and receptor tyrosine kinases (RTKs), enabling bidirectional mechanical signaling and modulation of survival pathways. ITGB4 activates PI3K/AKT and Ras-MAPK cascades, influencing epithelial differentiation, wound healing, and cancer progression. Mutations in ITGB4 cause junctional epidermolysis bullosa (JEB) with pyloric atresia, while its overexpression correlates with aggressive carcinomas, including triple-negative breast and pancreatic cancers. Emerging therapeutic strategies target ITGB4-mediated RTK crosstalk in tumors, with preclinical studies evaluating monoclonal antibodies and kinase inhibitors to disrupt its pro-metastatic signaling networks.