title: Oncogenic role of leptin and Notch interleukin-1 leptin crosstalk outcome in cancer.
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.
authors.affiliation: 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.
authors.forename: Crystal C
authors.initials: CC
authors.lastname: Lipsey
authors.affiliation: 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.
authors.forename: Adriana
authors.initials: A
authors.lastname: Harbuzariu
authors.affiliation: 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.
authors.forename: Danielle
authors.initials: D
authors.lastname: Daley-Brown
authors.affiliation: 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.
authors.forename: Ruben R
authors.initials: RR
authors.lastname: Gonzalez-Perez
keywords: Breast cancer; Endometrial cancer; Leptin; Notch, interleukin-1 and leptin crosstalk outcome; Obesity; Pancreatic cancer