title: Adiponectin inhibits leptin-induced oncogenic signalling in oesophageal cancer cells by activation of PTP1B.
abstract: Obesity is characterised by hyperleptinaemia and hypoadiponectinaemia and these metabolic abnormalities may contribute to the progression of several obesity-associated cancers including oesophageal adenocarcinoma (OAC). We have examined the effects of leptin and adiponectin on OE33 OAC cells. Leptin stimulated proliferation, invasion and migration and inhibited apoptosis in a STAT3-dependant manner. Leptin-stimulated MMP-2 secretion in a partly STAT3-dependent manner and MMP-9 secretion via a STAT3-independent pathway. Adiponectin inhibited leptin-induced proliferation, migration, invasion, MMP secretion and reduced the anti-apoptotic effects: these effects of adiponectin were ameliorated by both a non-specific tyrosine phosphatase inhibitor and a specific PTP1B inhibitor. Adiponectin reduced leptin-stimulated JAK2 activation and STAT3 transcriptional activity in a PTP1B-sensitive manner and adiponectin increased both PTP1B protein and activity. We conclude that adiponectin restrains leptin-induced signalling and pro-carcinogenic behaviour by inhibiting the early events in leptin-induced signal transduction by activating PTP1B. Relative adiponectin deficiency in obesity may contribute to the promotion of OAC.
authors.affiliation: Department of Gastroenterology, Norfolk and Norwich University Hospital, Norwich NR4 7UZ, UK; Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, UK. Electronic address: i.beales@uea.ac.uk.
authors.forename: Ian L P
authors.initials: ILP
authors.lastname: Beales
authors.affiliation: Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, UK.
authors.forename: Carla
authors.initials: C
authors.lastname: Garcia-Morales
authors.affiliation: Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, UK.
authors.forename: Olorunseun O
authors.initials: OO
authors.lastname: Ogunwobi
authors.affiliation: Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, UK.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Mutungi
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D052242:Adiponectin; D020738:Leptin; D050796:STAT3 Transcription Factor; D053614:Janus Kinase 2; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D020782:Matrix Metalloproteinases
keywords: 3-(4,5-dimethylthiazol-2-y-l)-2, 5-diphenyltetrazolium bromide; Adipo; Adiponectin; Barrett’s oesophagus; BrdU; ELISA; JAK; Leptin; MMP; MTT; OAC; Obesity; PTP; PTP1N; STAT3; adiponectin; bromodeoxyuridine; enzyme-linked immunoabsorbant assay; janus kinase; matrix metalloproteinase; oesophageal adenocarcinoma; protein tyrosine phosphatase; signal transducer and activator of transcription 3