title: LPA receptor heterodimerizes with CD97 to amplify LPA-initiated RHO-dependent signaling and invasion in prostate cancer cells.
abstract: 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.
authors: Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors: Yvona
authors: Y
authors: Ward
authors: Ross
authors: R
authors: Lake
authors: Juan Juan
authors: JJ
authors: Yin
authors: Christopher D
authors: CD
authors: Heger
authors: Mark
authors: M
authors: Raffeld
authors: Paul K
authors: PK
authors: Goldsmith
authors: Maria
authors: M
authors: Merino
authors: Kathleen
authors: K
authors: Kelly
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D018450:Disease Progression; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: C095004:ADGRE5 protein, human; D015703:Antigens, CD; D008246:Lysophospholipids; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D006160:Guanosine Triphosphate; D048049:Extracellular Signal-Regulated MAP Kinases; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020742:rhoA GTP-Binding Protein; C032881:lysophosphatidic acid