Shenyang Medical College, Key Laboratory of Environmental Pollution and Microecology of Liaoning Province , No.146 North Huanghe St, Huanggu Dis, Shenyang City, Liaoning Pro 110034 , PR China
Expert Opin Ther Targets. 2014 Aug;18(8):961-71. doi: 10.1517/14728222.2014.926889. Epub 2014 Jun 19.
Obesity is characterized by high secretion of several cytokines from adipose tissue and is a recognized risk factor for many cancers. Among these cytokines, leptin mainly produced by adipose tissue and cancer cells is the most studied adipokine. Leptin is an activator of cell proliferation, an antiapoptotic molecule and inducer of cancer stem cells in many cell types, and its critical roles in obesity-related tumorigenesis are based on its oncogenic, mitogenic, pro-inflammatory and pro-angiogenic actions.
These leptin-induced signals and action are critical for their biological effects on energy balance, adiposity, endocrine systems, immunity, angiogenesis as well as oncogenesis. This review focuses on the up-to-date knowledge on the oncogenic role of leptin signaling, clinical significance and specific drug target development in colorectal cancer (CRC). Additionally, leptin-induced angiogenic ability and molecular mechanisms in CRC cells are discussed.
Stringent binding affinity of leptin/Ob-R and overexpression of leptin/Ob-R and their targets in cancer cells make it a unique drug target for prevention and treatment of CRC, particularly in obesity colorectal patients.
肥胖的特征是脂肪组织分泌大量细胞因子，是许多癌症的公认危险因素。在这些细胞因子中，瘦素主要由脂肪组织和癌细胞产生，是研究最多的脂肪因子。瘦素是许多细胞类型中细胞增殖的激活剂、抗凋亡分子和癌症干细胞的诱导剂，其在肥胖相关肿瘤发生中的关键作用基于其致癌、有丝分裂原、促炎和促血管生成作用。
这些瘦素诱导的信号和作用对于其在能量平衡、肥胖、内分泌系统、免疫、血管生成以及肿瘤发生中的生物学效应至关重要。本综述重点介绍了瘦素信号在结直肠癌（CRC）中的致癌作用、临床意义和特定药物靶点开发的最新知识。此外，还讨论了瘦素诱导的 CRC 细胞的血管生成能力和分子机制。
瘦素/Ob-R 的严格结合亲和力和瘦素/Ob-R 及其在癌细胞中的靶标的过度表达，使其成为预防和治疗 CRC 的独特药物靶点，特别是在肥胖的结直肠癌患者中。
