Cadherin-11 binds to PDGFRβ and enhances cell proliferation and tissue regeneration via the PDGFR-AKT signaling axis

Abstract

Intercellular adhesion through homotypic interaction between cadherins regulates multiple cellular processes including cytoskeletal organization, proliferation, and survival. In this paper, we provide evidence that cadherin-11 (CDH11) binds to and promotes cell proliferation both in vitro and in vivo in synergy with the platelet-derived growth factor receptor beta (PDGFRβ). Engagement of CDH11 increased the sensitivity of cells to PDGF-BB by 10- to 100-fold, resulting in rapid and sustained phosphorylation of AKT, ultimately promoting and cell proliferation and tissue regeneration. Indeed, wound healing experiments showed that healing was severely compromised in Cdh11−/− mice, as evidenced by significantly decreased proliferation, AKT phosphorylation, and extracellular matrix (ECM) synthesis of dermal cells. Our results shed light into understanding how intercellular adhesion can promote cell proliferation and may have implications for tissue regeneration and cancer progression.