Hashmi Sarwar, Wang Yi, Suman Devi S, Parhar Ranjit S, Collison Kate, Conca Walter, Al-Mohanna Futwan, Gaugler Randy
Developmental Biology, Center for Vector Biology, Rutgers University, New Brunswick, NJ 08901, United States.
Developmental Biology, Center for Vector Biology, Rutgers University, New Brunswick, NJ 08901, United States.
Biochim Biophys Acta. 2015 Feb;1850(2):352-64. doi: 10.1016/j.bbagen.2014.11.004. Epub 2014 Nov 12.
Lipid metabolism dysfunction leading to excess fat deposits (obesity) may cause tumor (cancer) development. Both obesity and cancer are the epicenter of important medical issues. Lipid metabolism and cell death/proliferation are controlled by biochemical and molecular pathways involving many proteins, and organelles; alteration in these pathways leads to fat accumulation or tumor growth. Mammalian Krüppel-like factors, KLFs play key roles in both lipid metabolism and tumor development.
Substantial epidemiological and clinical studies have established strong association of obesity with a number of human cancers. However, we need more experimental verification to determine the exact role of this metabolic alteration in the context of tumor development. A clear understanding of molecules, pathways and the mechanisms involved in lipid metabolism and cell death/proliferation will have important implications in pathogenesis, and prevention of these diseases.
The regulatory role of KLFs, in both cell death/proliferation and lipid metabolism suggests a common regulation of both processes. This provides an excellent model for delivering a precise understanding of the mechanisms linking altered expression of KLFs to obesity and tumor development.
Currently, mouse and rats are the models of choice for investigating disease mechanisms and pharmacological therapies but a genetic model is needed for a thorough examination of KLF function in vivo during the development of an organism. The worm Caenorhabditis elegans is an ideal model to study the connectivity between lipid metabolism and cell death/proliferation.
脂质代谢功能障碍导致脂肪过度沉积（肥胖），可能会引发肿瘤（癌症）的发展。肥胖和癌症都是重要医学问题的核心。脂质代谢以及细胞死亡/增殖受涉及众多蛋白质和细胞器的生化及分子途径调控；这些途径的改变会导致脂肪堆积或肿瘤生长。哺乳动物的Krüppel样因子（KLFs）在脂质代谢和肿瘤发展中均发挥关键作用。
大量的流行病学和临床研究已证实肥胖与多种人类癌症之间存在密切关联。然而，我们需要更多的实验验证来确定这种代谢改变在肿瘤发展过程中的确切作用。清晰了解脂质代谢以及细胞死亡/增殖所涉及的分子、途径和机制，对于这些疾病的发病机制及预防具有重要意义。
KLFs在细胞死亡/增殖和脂质代谢方面的调控作用表明这两个过程存在共同调控。这为精准理解将KLFs表达改变与肥胖及肿瘤发展联系起来的机制提供了一个绝佳模型。
目前，小鼠和大鼠是研究疾病机制及药物治疗的首选模型，但在生物体发育过程中全面研究KLF功能需要一个遗传模型。秀丽隐杆线虫是研究脂质代谢与细胞死亡/增殖之间联系的理想模型。
