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Cadherin‐11 binds to PDGFRβ and enhances cell proliferation and tissue regeneration via the PDGFR‐AKT signaling axis
Author(s) -
Liu Yayu,
Lei Pedro,
Row Sindhu,
Andreadis Stelios T.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902613r
Subject(s) - platelet derived growth factor receptor , microbiology and biotechnology , cadherin , protein kinase b , regeneration (biology) , cell growth , signal transduction , cell , chemistry , receptor , biology , growth factor , biochemistry
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.