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

•Leptin stimulated oncogenic behaviour in oesophageal adenocarcinoma cells.•Adiponectin inhibited leptin-induced signal transduction and oncogenic behaviour.•Adiponectin independently increased PTP1B activity and PTP1B protein expression.•Inhibition of leptin-signal transduction by adiponectin was PTP1B-dependent.•Interaction of adipokines at the cellular level may contribute to oesophageal carcinogenesis. 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.