Adiponectin inhibits leptin-induced oncogenic signalling in oesophageal cancer cells by activation of PTP1B

Beales, Ian L P, Garcia-Morales, Carla, Ogunwobi, Olorunseun O and Mutungi, Gabriel (2014) Adiponectin inhibits leptin-induced oncogenic signalling in oesophageal cancer cells by activation of PTP1B. Molecular and Cellular Endocrinology, 382 (1). pp. 150-8.

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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.

Item Type: Article
Additional Information: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
University of East Anglia > Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
University of East Anglia > Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Science
Depositing User: Pure Connector
Date Deposited: 16 Dec 2013 15:10
Last Modified: 25 Jul 2018 09:10
URI: https://ueaeprints.uea.ac.uk/id/eprint/45964
DOI: 10.1016/j.mce.2013.08.013

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