title: The role of the obestatin/GPR39 system in human gastric adenocarcinomas.
abstract: Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor were reported to be involved in the control of mitogenesis of gastric cancer cell lines; however, the relationship between the obestatin/GPR39 system and gastric cancer progression remains unknown. In the present study, we determined the expression levels of the obestatin/GPR39 system in human gastric adenocarcinomas and explored their potential functional roles. Twenty-eight patients with gastric adenocarcinomas were retrospectively studied, and clinical data were obtained. The role of obestatin/GPR39 in gastric cancer progression was studied in vitro using the human gastric adenocarcinoma AGS cell line. Obestatin exogenous administration in these GPR39-bearing cells deregulated the expression of several hallmarks of the epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, obestatin signaling promoted phenotypic changes via GPR39, increasingly impacting on the cell morphology, proliferation, migration and invasion of these cells. In healthy human stomachs, obestatin expression was observed in the neuroendocrine cells and GPR39 expression was localized mainly in the chief cells of the oxyntic glands. In human gastric adenocarcinomas, no obestatin expression was found; however, an aberrant pattern of GPR39 expression was discovered, correlating to the dedifferentiation of the tumor. Altogether, our data strongly suggest the involvement of the obestatin/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas and highlight the potential usefulness of GPR39 as a prognostic marker in gastric cancer.
authors.affiliation: Área de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS), Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, Spain.
authors.forename: Begoña O
authors.initials: BO
authors.lastname: Alén
authors.affiliation: Área de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS), Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, Spain.
authors.forename: Saúl
authors.initials: S
authors.lastname: Leal-López
authors.affiliation: IDIS, CHUS, Santiago de Compostela, Spain.|Servicio de Anatomía Patológica, CHUS, SERGAS, Santiago de Compostela, Spain.
authors.forename: María Otero
authors.initials: MO
authors.lastname: Alén
authors.affiliation: IDIS, CHUS, Santiago de Compostela, Spain.|Servicio de Anatomía Patológica, CHUS, SERGAS, Santiago de Compostela, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Viaño
authors.affiliation: Servicio de Anatomía Patológica, CHUS, SERGAS, Santiago de Compostela, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: García-Castro
authors.affiliation: Área de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS), Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, Spain.
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Mosteiro
authors.affiliation: IDIS, CHUS, Santiago de Compostela, Spain.|Servicio de Anatomía Patológica, CHUS, SERGAS, Santiago de Compostela, Spain.|Departamento de Ciencias Morfológicas, Universidad de Santiago de Compostela (USC), Santiago de Compostela, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Beiras
authors.affiliation: Área de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS), Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, Spain.|Departamento de Medicina, USC, Santiago de Compostela, Spain.
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Casanueva
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, Spain.|IDIS, CHUS, Santiago de Compostela, Spain.|Departamento de Ciencias Morfológicas, Universidad de Santiago de Compostela (USC), Santiago de Compostela, Spain.
authors.forename: Rosalía
authors.initials: R
authors.lastname: Gallego
authors.affiliation: IDIS, CHUS, Santiago de Compostela, Spain.|Servicio de Anatomía Patológica, CHUS, SERGAS, Santiago de Compostela, Spain.|Departamento de Ciencias Morfológicas, Universidad de Santiago de Compostela (USC), Santiago de Compostela, Spain.
authors.forename: Tomás
authors.initials: T
authors.lastname: García-Caballero
authors.affiliation: Área de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS), Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, Spain.
authors.forename: Jesús P
authors.initials: JP
authors.lastname: Camiña
authors.affiliation: Área de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS), Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Pazos
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008297:Male; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: C495797:GPR39 protein, human; D043562:Receptors, G-Protein-Coupled
keywords: GPR39; adenocarcinoma; obestatin; stomach