Laminin 332 in cancer: When the extracellular matrix turns signals from cell anchorage to cell movement

Laminin 332 is crucial in the biology of epithelia. This large extracellular matrix protein consists of the heterotrimeric assembly of three subunits - alpha 3, beta 3, and gamma 2 - and its multifunctionality relies on a number of extracellular proteolytic processing events. Laminin 332 is central to normal epithelium homeostasis by sustaining cell adhesion, polarity, proliferation, and differentiation. It also supports a major function in epithelial tissue formation, repair, and regeneration by buttressing cell migration and survival and basement membrane assembly. Interest in this protein increased after the discovery that its expression is perturbed in tumor cells, cancer-associated fibroblasts, and the tumor microenvironment. This review summarizes current knowledge regarding the established involvement of the laminin 332 gamma 2 chain in tumor invasiveness and discusses the role of its alpha 3 and beta 3 subunits.