Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Methodol. Mar 26, 2016; 6(1): 43-55
Published online Mar 26, 2016. doi: 10.5662/wjm.v6.i1.43
Oncogenic role of leptin and Notch interleukin-1 leptin crosstalk outcome in cancer
Crystal C Lipsey, Adriana Harbuzariu, Danielle Daley-Brown, Ruben R Gonzalez-Perez
Crystal C Lipsey, Adriana Harbuzariu, Danielle Daley-Brown, Ruben R Gonzalez-Perez, Department of Microbiology, Biochemistry and Immunology, Graduate Education in Biomedical Sciences, Morehouse School of Medicine, Atlanta, GA 30310, United States
Author contributions: All authors contributed to this manuscript.
Supported by The National Cancer Institute at the National Institutes of Health (NIH 1R41 CA183399-01A1, 5U54 CA118638 Pilot Project Award and UAB/UMN SPORE in Pancreatic Cancer) and the Congressionally Directed Medical Research Programs-Department of Defense (CDMRP DOD W81XWH-13-1-0382) to Gonzalez-Perez RR; and NCI S21 MD000101, 5G12 MD0076021, G12 RR026250-03, NIH RR03034 and 1C06 RR18386 to Morehouse School of Medicine, and the National Center for Advancing Translational Sciences of the NIH Award 5T32HL103104-04 (MPI) to Daley-Brown D.
Conflict-of-interest statement: The authors of this manuscript indicate to have no potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ruben R Gonzalez-Perez, PhD, Department of Microbiology, Biochemistry and Immunology, Graduate Education in Biomedical Sciences, Morehouse School of Medicine, 720 Westview Drive, Hugh Gloster Suite 329, Atlanta, GA 30310, United States. rgonzalez@msm.edu
Telephone: +1-404-7521581
Received: August 29, 2015
Peer-review started: September 7, 2015
First decision: October 8, 2015
Revised: January 30, 2016
Accepted: March 7, 2016
Article in press: March 9, 2016
Published online: March 26, 2016
Abstract

Obesity is a global pandemic characterized by high levels of body fat (adiposity) and derived-cytokines (i.e., leptin). Research shows that adiposity and leptin provide insight on the link between obesity and cancer progression. Leptin’s main function is to regulate energy balance. However, obese individuals routinely develop leptin resistance, which is the consequence of the breakdown in the signaling mechanism controlling satiety resulting in the accumulation of leptin. Therefore, leptin levels are often chronically elevated in human obesity. Elevated leptin levels are related to higher incidence, increased progression and poor prognosis of several human cancers. In addition to adipose tissue, cancer cells can also secrete leptin and overexpress leptin receptors. Leptin is known to act as a mitogen, inflammatory and pro-angiogenic factor that induces cancer cell proliferation and tumor angiogenesis. Moreover, leptin signaling induces cancer stem cells, which are involved in cancer recurrence and drug resistance. A novel and complex signaling crosstalk between leptin, Notch and interleukin-1 (IL-1) [Notch, IL-1 and leptin crosstalk outcome (NILCO)] seems to be an important driver of leptin-induced oncogenic actions. Leptin and NILCO signaling mediate the activation of cancer stem cells that can affect drug resistance. Thus, leptin and NILCO signaling are key links between obesity and cancer progression. This review presents updated data suggesting that adiposity affects cancer incidence, progression, and response to treatment. Here we show data supporting the oncogenic role of leptin in breast, endometrial, and pancreatic cancers.

Keywords: Obesity, Leptin, Breast cancer, Endometrial cancer, Pancreatic cancer, Notch, interleukin-1 and leptin crosstalk outcome

Core tip: Obesity is a global pandemic and a risk factor for a number of cancers. Obesity is characterized by high levels of body fat (adiposity) and leptin. Research shows that leptin and its oncogenic crosstalk Notch, interleukin-1 and leptin crosstalk outcome (NILCO) provide insight on the link between obesity and cancer progression. Thus, leptin and NILCO can act as mitogenic, inflammatory, and angiogenic cues promoting the progression of cancer, cancer stem cells, and drug resistance. This review shows updated information on leptin and NILCO’s oncogenic roles in breast, endometrial, and pancreatic cancers.