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LPA receptor heterodimerizes with CD97 to amplify LPA-initiated RHO-dependent signaling and invasion in prostate cancer cells.
Ward, Yvona; Lake, Ross; Yin, Juan Juan; Heger, Christopher D; Raffeld, Mark; Goldsmith, Paul K; Merino, Maria; Kelly, Kathleen.
Afiliação
  • Ward Y; Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.
Cancer Res ; 71(23): 7301-11, 2011 Dec 01.
Article em En | MEDLINE | ID: mdl-21978933
CD97, an adhesion-linked G-protein-coupled receptor (GPCR), is induced in multiple epithelial cancer lineages. We address here the signaling properties and the functional significance of CD97 expression in prostate cancer. Our findings show that CD97 signals through Gα12/13 to increase RHO-GTP levels. CD97 functioned to mediate invasion in prostate cancer cells, at least in part, by associating with lysophosphatidic acid receptor 1 (LPAR1), leading to enhanced LPA-dependent RHO and extracellular signal-regulated kinase activation. Consistent with its role in invasion, depletion of CD97 in PC3 cells resulted in decreased bone metastasis without affecting subcutaneous tumor growth. Furthermore, CD97 heterodimerized and functionally synergized with LPAR1, a GPCR implicated in cancer progression. We also found that CD97 and LPAR expression were significantly correlated in clinical prostate cancer specimens. Taken together, these findings support the investigation of CD97 as a potential therapeutic cancer target.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Lisofosfolipídeos / Antígenos CD / Proteína rhoA de Ligação ao GTP / Receptores de Ácidos Lisofosfatídicos Limite: Humans / Male Idioma: En Revista: Cancer Res Ano de publicação: 2011 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Lisofosfolipídeos / Antígenos CD / Proteína rhoA de Ligação ao GTP / Receptores de Ácidos Lisofosfatídicos Limite: Humans / Male Idioma: En Revista: Cancer Res Ano de publicação: 2011 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos