Laminin-binding integrins

Laminin-binding integrins, primarily comprising the heterodimers alpha-3/beta-1, alpha-6/beta-1, alpha-6/beta-4, and alpha-7/beta-1, are essential cell-surface receptors that mediate the attachment of epithelial and muscle cells to the laminin-rich basement membrane (Nishiuchi et al., 2006). These receptors are critical for maintaining tissue architecture and regulating diverse cellular processes, including survival, proliferation, and migration, through the activation of intracellular signaling cascades like the PI3K and MAPK pathways (Stewart & O'Connor, 2015). The alpha-6/beta-4 integrin is particularly notable for its role in forming hemidesmosomes, which provide mechanical stability to the skin by linking the extracellular matrix to the intermediate filament cytoskeleton (Wilhelmsen et al., 2006). In pathological contexts, these integrins are frequently hijacked by cancer cells to promote invasion, metastasis, and the survival of cancer stem cells, making them attractive targets for therapeutic intervention (Ramovs et al., 2017). While several monoclonal antibodies and peptides targeting these integrins are under investigation in preclinical and early clinical studies, no specific inhibitors have yet reached widespread clinical approval. Potential safety concerns for targeting this class include the risk of skin fragility and impaired wound healing, mirroring the phenotypes seen in genetic deficiencies like junctional epidermolysis bullosa (Has et al., 2020).

Other names

Alpha-6 integrin familyLaminin receptorsCD49f-containing integrinsVLA-6Integrin alpha-6 family

Antagonism of laminin binding to the extracellular domain of the integrin heterodimer, thereby preventing cell adhesion and disrupting pro-survival and pro-migratory signaling pathways such as PI3K/Akt and FAK/Src.