Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran.
Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Cell Oncol (Dordr). 2019 Jun;42(3):243-260. doi: 10.1007/s13402-019-00428-0. Epub 2019 Mar 15.
Increasing evidence indicates that obesity is associated with tumor development and progression. Leptin is an adipocyte-related hormone with a key role in energy metabolism and whose circulating levels are elevated in obesity. The effect of leptin on cancer progression and metastasis and its underlying mechanisms are still unclear. Leptin can impact various steps in tumor metastasis, including epithelial-mesenchymal transition, cell adhesion to the extracellular matrix (ECM), and proteolysis of ECM components. To do so, leptin binds to its receptor (OB-Rb) to activate signaling pathways and downstream effectors that participate in tumor cell invasion as well as distant metastasis.
In this review, we describe metastasis steps in detail and characterize metastasis-related molecules activated by leptin, which may help to develop a roadmap that guides future work. In addition, we conclude that a profound understanding of the fundamental molecular processes that contribute to leptin-induced metastasis may pave the way for the development of new prognostic molecules and appropriate approaches to the treatment of obesity-related cancers.
越来越多的证据表明,肥胖与肿瘤的发生和发展有关。瘦素是一种与脂肪细胞相关的激素,在能量代谢中起着关键作用,其循环水平在肥胖症中升高。瘦素对癌症进展和转移的影响及其潜在机制尚不清楚。瘦素可以影响肿瘤转移的各个步骤,包括上皮-间充质转化、细胞与细胞外基质(ECM)的黏附以及 ECM 成分的蛋白水解。为此,瘦素与它的受体(OB-Rb)结合,激活参与肿瘤细胞侵袭和远处转移的信号通路和下游效应子。
在这篇综述中,我们详细描述了转移的步骤,并描述了瘦素激活的与转移相关的分子,这可能有助于制定未来工作的路线图。此外,我们得出结论,深入了解导致瘦素诱导转移的基本分子过程,可能为开发新的预后分子和治疗肥胖相关癌症的适当方法铺平道路。