Role of the long form leptin receptor and of the STAT3 signaling pathway in colorectal cancer progression

  • Authors: Takashi Uchiyama, Hirokazu Takahashi, Hiroki Endo, Michiko Sugiyama, Eiji Sakai, Kunihiro Hosono, Yoji Nagashima, Yoshiaki Inayama, Koichiro Wada, Yoshitaka Hippo, Atsushi Nakajima
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  • Published online on: Wednesday, June 29, 2011
  • Pages: 935-940
  • DOI: 10.3892/ijo.2011.1105

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 carcino­genesis 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.
Journal Cover

October 2011
Volume 39 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2012 Impact Factor: 2.657
Ranked #31/196 Oncology
(total number of cites)

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APA
Uchiyama, T., Takahashi, H., Endo, H., Sugiyama, M., Sakai, E., Hosono, K., Nagashima, Y., Inayama, Y., Wada, K., Hippo, Y., & Nakajima, A. (2011). Role of the long form leptin receptor and of the STAT3 signaling pathway in colorectal cancer progression. International Journal of Oncology, 39(4), 935-940.
MLA
Uchiyama, Takahashi, Endo, Sugiyama, Sakai, Hosono, Nagashima, Inayama, Wada, Hippo, and Atsushi Nakajima. "Role of the long form leptin receptor and of the STAT3 signaling pathway in colorectal cancer progression." International Journal of Oncology International Journal of Oncology 39.4 (2011): 935-940.
Chicago
Uchiyama, Takahashi, Endo, Sugiyama, Sakai, Hosono, Nagashima, Inayama, Wada, Hippo, and Atsushi Nakajima. "Role of the long form leptin receptor and of the STAT3 signaling pathway in colorectal cancer progression." International Journal of Oncology International Journal of Oncology 39 no. 4 (2011): 935-940.