title: Prometastatic GPCR CD97 is a direct target of tumor suppressor microRNA-126.
abstract: Tumor suppressor microRNA-126 (miR-126) is often down-regulated in cancer cells, and its overexpression is found to inhibit cancer metastasis. To elucidate the mechanism of tumor suppression by miR-126, we analyzed the proteomic response to miR-126 overexpression in the human metastatic breast cancer cell line MDA-MB-231. To acquire quantitative, time-resolved information, we combined two complementary proteomic methods, BONCAT and SILAC. We discovered a new direct target of miR-126: CD97, a pro-metastatic G-protein-coupled receptor (GPCR) that has been reported to promote tumor cell invasion, endothelial cell migration, and tumor angiogenesis. This discovery establishes a link between down-regulation of miR-126 and overexpression of CD97 in cancer and provides new mechanistic insight into the role of miR-126 in inhibiting both cell-autonomous and non-cell-autonomous cancer progression.
authors.affiliation: Division of Chemistry and Chemical Engineering, MC 210-41, California Institute of Technology , 1200 East California Boulevard, Pasadena, California 91125, United States.
authors.forename: Ying Y
authors.initials: YY
authors.lastname: Lu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sweredoski
authors.forename: David
authors.initials: D
authors.lastname: Huss
authors.forename: Rusty
authors.initials: R
authors.lastname: Lansford
authors.forename: Sonja
authors.initials: S
authors.lastname: Hess
authors.forename: David A
authors.initials: DA
authors.lastname: Tirrell
mesh_terms: D015703:Antigens, CD / Q000235:genetics*; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D040901:Proteomics; D043562:Receptors, G-Protein-Coupled; D015854:Up-Regulation
chemical_list: C095004:ADGRE5 protein, human; D015703:Antigens, CD; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D043562:Receptors, G-Protein-Coupled