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

Author:
Beales, Ian L.P., Garcia-Morales, Carla, Ogunwobi, Olorunseun O., Mutungi, Gabriel
Source:
Molecular and Cellular Endocrinology 2014 v.382 pp. 150-158
ISSN:
0303-7207
Subject:
adenocarcinoma, adiponectin, apoptosis, leptin, neoplasm cells, non-specific protein-tyrosine kinase, obesity, secretion, signal transduction, transcription (genetics), tyrosine
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.
Agid:
5522473