GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis

Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9023-8. doi: 10.1073/pnas.0602681103. Epub 2006 Jun 6.

Abstract

The survival and growth of tumor cells in a foreign environment is considered a rate-limiting step during metastasis. To identify genes that may be essential for this process, we isolated highly metastatic variants from a poorly metastatic human melanoma cell line and performed expression analyses of metastases and primary tumors from these cells. GPR56 is among the genes markedly down-regulated in the metastatic variants. We show that overexpression of GPR56 suppresses tumor growth and metastasis, whereas reduced expression of GPR56 enhances tumor progression. Levels of GPR56 do not correlate with growth rate in vitro, suggesting that GPR56 may mediate growth suppression by interaction with a component in the tumor microenvironment in vivo. We show that GPR56 binds specifically to tissue transglutaminase, TG2, a widespread component of tissue and tumor stroma previously implicated as an inhibitor of tumor progression. We discuss the mechanisms whereby GPR56-TG2 interactions may suppress tumor growth and metastasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • GTP-Binding Proteins
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Melanoma* / metabolism
  • Melanoma* / pathology
  • Mice
  • Molecular Sequence Data
  • Neoplasm Metastasis*
  • Protein Binding
  • Protein Glutamine gamma Glutamyltransferase 2
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Transglutaminases / metabolism*

Substances

  • ADGRG1 protein, human
  • Receptors, G-Protein-Coupled
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins