Gong Y, Dou L-J, Liang J
Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical College; The Affiliated XuZhou Hospital of Medical College of Southeast University, Jiangsu, China.
Eur Rev Med Pharmacol Sci. 2014 Oct;18(19):2808-20.
Obesity has long been suspected to be a risk factor for cancer. The relationship between body fat deposition and the pathogenesis of cancer has been the subject of many studies, however, no clear consensus has emerged linking these two biological processes. Recent epidemiological studies showed a strong association between cancer-related deaths and increased body-mass index. In fact, obesity has been identified as a cause for oesophageal, colon, uterine, kidney and post-menopausal breast cancers and also as a significant risk factor for the cancers of prostate, pancreas and non-Hodgkin lymphoma. Approximately 16-20% of cancer deaths in women and 14% of cancer deaths in men were found to be due to obesity. It is also recognized that there is a positive relationship between type-2 diabetes associated hyperinsulinemia and cancer incidence. Though the recent annual report in US finds that the incidence and mortality rates for many cancers have dropped in 2003 since 1975, this decline is mostly due to a substantial decrease in tobacco use among men. However, during the same period the rise in the prevalence of obesity might have contributed to the increased risk and incidence of prostate, liver, kidney, oesophageal and breast cancers. Whether the elevated cancer risk in obesity arises from similar modulation of parallel signaling/metabolic pathways during adipogenesis and oncogenesis has not been hitherto addressed. In this Review we would like to bring out the similarities between adipogenesis and oncogenesis and how this relationship at molecular level may be relevant for the development of effective therapeutics for obesity, diabetes and cancer. While adipogenesis is the process of formation of mature adipocytes or fat cells under normal physiological conditions, oncogenesis is a pathological process, which results in the uncontrolled growth of cells leading to cancer. Though, both these processes at surface seem to be totally different, we believe that there are important common denominators for these processes that need to be recognized. We will discuss the role of two such underlying factors - (1) malonyl-CoA, an important regulator of fatty acid metabolism and (2) triglyceride/free fatty acid (TG/FFA) cycling which is central to the generation of multiple signals for controlling various metabolic, physiological and signaling pathways in the cell.
长期以来，肥胖一直被怀疑是癌症的一个风险因素。体脂沉积与癌症发病机制之间的关系一直是许多研究的主题，然而，尚未就这两个生物学过程之间的联系达成明确共识。最近的流行病学研究表明，癌症相关死亡与体重指数增加之间存在密切关联。事实上，肥胖已被确定为食管癌、结肠癌、子宫癌、肾癌和绝经后乳腺癌的一个病因，也是前列腺癌、胰腺癌和非霍奇金淋巴瘤的一个重要风险因素。据发现，女性约16 - 20%的癌症死亡和男性14%的癌症死亡归因于肥胖。人们还认识到，2型糖尿病相关的高胰岛素血症与癌症发病率之间存在正相关关系。尽管美国最近的年度报告发现，自1975年以来，2003年许多癌症的发病率和死亡率有所下降，但这种下降主要是由于男性吸烟率大幅下降。然而，在同一时期，肥胖患病率的上升可能导致了前列腺癌、肝癌、肾癌、食管癌和乳腺癌的风险及发病率增加。肥胖中癌症风险升高是否源于脂肪生成和肿瘤发生过程中平行信号/代谢途径的类似调节，迄今尚未得到解决。在本综述中，我们将阐述脂肪生成和肿瘤发生之间的相似之处，以及这种分子水平的关系如何可能与肥胖、糖尿病和癌症有效治疗方法的开发相关。脂肪生成是在正常生理条件下成熟脂肪细胞或脂肪形成的过程，而肿瘤发生是一个病理过程，它导致细胞不受控制地生长从而引发癌症。尽管这两个过程表面上似乎完全不同，但我们认为这些过程存在重要的共同特征，需要加以认识。我们将讨论两个这样的潜在因素的作用——（1）丙二酰辅酶A，脂肪酸代谢的重要调节因子，以及（2）甘油三酯/游离脂肪酸（TG/FFA）循环，它对于产生控制细胞内各种代谢、生理和信号通路的多种信号至关重要。
