Getting a grip on adhesion: Cadherin switching and collagen signaling

Epithelial-mesenchymal transition (EMT) is a developmental biological process that is hijacked during tumor progression. Cadherin switching, which disrupts adherens junctions and alters cadherin-associated signaling pathways, is common during EMT. In many tumors, substantial extracellular matrix (ECM) is deposited. Collagen is the most abundant ECM constituent and it mediates specific signaling pathways by binding to integrins and discoidin domain receptors (DDRs). The interaction of the collagen receptors results in activation of signaling pathways that promote tumor progression including an induction of the cadherin switching. DDR inhibitors have demonstrated anticancer therapeutic efficacy preclinically by inhibiting the collagen signaling. Understanding how collagen signaling impacts cellular processes including EMT and cadherin switching is of great interest especially given the strong interest in stromal targeted therapies for desmoplastic cancers.