Lipsey Crystal C, Harbuzariu Adriana, Daley-Brown Danielle, Gonzalez-Perez Ruben R
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.
World J Methodol. 2016 Mar 26;6(1):43-55. doi: 10.5662/wjm.v6.i1.43.
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.
肥胖是一种全球性的流行病，其特征是体内脂肪（肥胖）和衍生细胞因子（即瘦素）水平较高。研究表明，肥胖和瘦素为肥胖与癌症进展之间的联系提供了线索。瘦素的主要功能是调节能量平衡。然而，肥胖个体通常会出现瘦素抵抗，这是控制饱腹感的信号机制失灵导致瘦素积累的结果。因此，在人类肥胖中，瘦素水平往往长期升高。瘦素水平升高与几种人类癌症的更高发病率、进展加快和预后不良有关。除脂肪组织外，癌细胞也能分泌瘦素并过度表达瘦素受体。已知瘦素可作为一种促分裂原、炎症因子和促血管生成因子，诱导癌细胞增殖和肿瘤血管生成。此外，瘦素信号传导可诱导癌症干细胞，而癌症干细胞与癌症复发和耐药性有关。瘦素、Notch和白细胞介素-1（IL-1）之间一种新的复杂信号串扰[Notch、IL-1和瘦素串扰结果（NILCO）]似乎是瘦素诱导致癌作用的重要驱动因素。瘦素和NILCO信号传导介导了可影响耐药性的癌症干细胞的激活。因此，瘦素和NILCO信号传导是肥胖与癌症进展之间的关键环节。本综述提供了最新数据，表明肥胖会影响癌症的发病率、进展及对治疗的反应。在此，我们展示了支持瘦素在乳腺癌、子宫内膜癌和胰腺癌中致癌作用的数据。
