Adiponectin inhibits leptin-induced oncogenic signalling in oesophageal cancer cells by activation of PTP1B.
Mol Cell Endocrinol
; 382(1): 150-158, 2014 Jan 25.
Article
em En
| MEDLINE
| ID: mdl-23994026
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.
Palavras-chave
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
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Esofágicas
/
Transdução de Sinais
/
Leptina
/
Adiponectina
/
Proteína Tirosina Fosfatase não Receptora Tipo 1
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article