摘要
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.
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.
基金
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)
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
the National Center for Advancing Translational Sciences of the NIH Award 5T32HL103104-04(MPI)to Daley-Brown D
