title: Holo-retinol-binding protein and its receptor STRA6 drive oncogenic transformation.
abstract: Vitamin A, retinol, circulates in blood bound to retinol-binding protein (RBP). At some tissues, RBP is recognized by STRA6, a plasma membrane protein that serves a dual role: it transports retinol from extracellular RBP into cells and it transduces a signaling cascade mediated by the Janus kinase JAK2 and the transcription factors STAT3 and STAT5. We show here that expression of RBP and STRA6 is markedly upregulated in human breast and colon tumors, that holo-RBP/STRA6 signaling promotes oncogenic properties, and that STRA6 expression is critical for tumor formation by colon carcinoma cells in vivo. The holo-RBP/STRA6 pathway also efficiently induces fibroblasts to undergo oncogenic transformation, rendering them highly tumorigenic. These data establish that holo-RBP and its receptor STRA6 are potent oncogenes and suggest that the pathway is a novel target for therapy of some human cancers.
authors.affiliation: Department of Cellular & Molecular Medicine, Lerner Research Institute, Cleveland Clinic, and Departments of Pharmacology and Nutrition, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Berry
authors.affiliation: Department of Cellular & Molecular Medicine, Lerner Research Institute, Cleveland Clinic, and Departments of Pharmacology and Nutrition, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Liraz
authors.initials: L
authors.lastname: Levi
authors.affiliation: Department of Cellular & Molecular Medicine, Lerner Research Institute, Cleveland Clinic, and Departments of Pharmacology and Nutrition, Case Western Reserve University School of Medicine, Cleveland, Ohio. noyn@ccf.org.
authors.forename: Noa
authors.initials: N
authors.lastname: Noy
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014801:Vitamin A / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D012177:Retinol-Binding Proteins; C519685:STRA6 protein, human; D014801:Vitamin A; C507924:JAK2 protein, human; D053614:Janus Kinase 2