GPR56 inhibits melanoma growth by internalizing and degrading its ligand TG2.

ABSTRACT: Excessive accumulation of extracellular matrix (ECM) is a hallmark of tumor microenvironment and plays active roles during tumor progression. How this process is regulated and whether it is reversible for cancer treatment are outstanding questions. The adhesion G protein-coupled receptor GPR56 inhibits melanoma growth and binds to tissue transglutaminase (TG2), a major crosslinking enzyme in ECM. To understand the function of TG2 in GPR56-mediated melanoma inhibition, we performed xenograft studies in immunodeficient Tg2(-/-) mice. Our results revealed an antagonistic relationship between GPR56 and TG2 in melanoma, although TG2 and its crosslinking activity promote melanoma growth, GPR56 antagonizes this effect by internalizing and degrading it. The negative regulation of TG2 by GPR56 asso

SUBMITTER: Yang L 

PROVIDER: S-EPMC3944670 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature