Braccini L, Ciraolo E, Martini M, Pirali T, Germena G, Rolfo K, Hirsch E
Department of Genetics, Biology and Biochemistry, Molecular Biotechnology Center, University of Torino, Torino, Italy.
Adv Biol Regul. 2012 Sep;52(3):389-405. doi: 10.1016/j.jbior.2012.04.002. Epub 2012 Apr 24.
Epidemiological studies have established a positive correlation between cancer and metabolic disorders, suggesting that aberrant cell metabolism is a common feature of nearly all tumors. To meet their demand of building block molecules, cancer cells switch to a heavily glucose-dependent metabolism. As insulin triggers glucose uptake, most tumors are or become insulin-dependent. However, the effects of insulin and of other similar growth factors are not only limited to metabolic control but also favor tumor growth by stimulating proliferation and survival. A key signaling event mediating these metabolic and proliferative responses is the activation of the phosphatidylinositol-3 kinases (PI3K) pathway. In this review, we will thus discuss the current concepts of tumor metabolism and the opportunity of PI3K-targeted therapies to exploit the "sweet tooth" of cancer cells.
流行病学研究已证实癌症与代谢紊乱之间存在正相关,这表明异常的细胞代谢是几乎所有肿瘤的一个共同特征。为了满足对构建分子的需求,癌细胞转向严重依赖葡萄糖的代谢。由于胰岛素触发葡萄糖摄取,大多数肿瘤是胰岛素依赖型的,或者会变成胰岛素依赖型。然而,胰岛素和其他类似生长因子的作用不仅限于代谢控制,还通过刺激增殖和存活来促进肿瘤生长。介导这些代谢和增殖反应的一个关键信号事件是磷脂酰肌醇-3激酶(PI3K)途径的激活。因此,在本综述中,我们将讨论肿瘤代谢的当前概念以及PI3K靶向治疗利用癌细胞“嗜甜”特性的机会。