title: Role of the long form leptin receptor and of the STAT3 signaling pathway in colorectal cancer progression.
abstract: Although a number of recent studies have reported the involvement of leptin in colorectal carcinogenesis, findings are contradictory and difficult to interpret. Our group has previously reported that leptin signaling might have an important role in the development of colorectal adenomas. In this study, we investigated leptin signaling in colorectal carcino-genesis focusing in particular on the differences in leptin signaling between colorectal adenoma and cancer. Whereas no significant differences in the serum leptin levels were observed among normal control subjects and adenoma/cancer patients, increased expression and activation of the long form leptin receptor (ObRL) was observed in colorectal adenoma and cancer tissues compared with the normal colorectal tissues. However, no significant differences were observed between the colorectal adenoma and cancer tissues. Significant increases in the phosphorylation levels of important molecules of the JAK/STAT signaling pathway, located downstream of leptin signaling, and transcriptional regulation of STAT3-downstream target molecules were observed in colorectal adenoma tissue compared with the findings in normal colorectal tissues. Furthermore, these changes were significantly more pronounced in colorectal cancer compared to colorectal adenoma tissues. This is the first analysis of leptin and JAK/STAT signaling in a human colorectal adenoma-carcinoma sequence. These results suggest that the STAT3-mediated leptin signaling through the activation of ObRL may be involved in colorectal carcinogenesis, both in adenoma formation and in the progression to cancer. STAT3 signaling in colorectal cancer may be mediated not only by leptin but by other factors.
authors: Division of Gastroenterology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Japan.
authors: Takashi
authors: T
authors: Uchiyama
authors: Hirokazu
authors: H
authors: Takahashi
authors: Hiroki
authors: H
authors: Endo
authors: Michiko
authors: M
authors: Sugiyama
authors: Eiji
authors: E
authors: Sakai
authors: Kunihiro
authors: K
authors: Hosono
authors: Yoji
authors: Y
authors: Nagashima
authors: Yoshiaki
authors: Y
authors: Inayama
authors: Koichiro
authors: K
authors: Wada
authors: Yoshitaka
authors: Y
authors: Hippo
authors: Atsushi
authors: A
authors: Nakajima
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism; D020738:Leptin / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020738:Leptin; D012333:RNA, Messenger; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053612:Janus Kinases