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Cancer's sweet tooth: the Janus effect of glucose metabolism in tumorigenesis
The Lancet. Feb 18-Feb 24, 2006.Vol.367, Iss. 9510; pg. 618, 4 pgs
Author: Houman Ashrafian.
Abstract
Despite Otto Warburg's 1931 Nobel Prize for his work affirming the role of metabolism in carcinogenesis, there has been little further interest in this association between metabolism and cancer. Disinterest has, in part, been attributable to the notion that Warburg's description of a relation between a shift to glycolysis in carcinogenesis may be an epiphenomenon rather than a mechanistic determinant. By studying the critical cellular energy sensor AMP-activated protein kinase (AMPK), I postulate that the association between intermediary metabolism and tumours varies over time. Through accumulation of carbohydrates and pan-inhibition of AMPK, premalignant tumours may gain a replicative advantage through the repression of senescence. Conversely, malignant tumours, with a defective tumour suppressor contingent, undergo a "glycolytic switch", in part by tolerating a degree of AMPK activation, to mitigate substrate limitation. I contend that this Janus-faced relation with intermediary metabolism contributes to carcinogenesis; if proven, this finding would have important implications for public health, in that it would lend support to the idea that prevention of obesity, and caloric restriction and exercise could reduce the predisposition to cancer.

癌症喜好甜食：肿瘤发生中葡萄糖代谢的两面效应

虽然Otto Warburg 因确定癌症发生中代谢的作用而获得1931年的诺贝尔奖，但科研人员对研究代谢和癌症之间的关系却少有关注。这部分归因于Warburg所提出的观点，即在癌症发生的代谢和癌症的关系中，糖酵解转变可能只是一种偶发现象而不是决定性机制。通过研究重要的细胞能量传感器AMP活化蛋白激酶(AMPK)，我假定了中间物代谢和肿瘤逐步改变之间的关系。通过碳水化合物（糖类）的积累和AMPK的完全抑制作用，癌变前的肿瘤可能通过对衰老的抑制来获得复制的优势。反之，具有缺陷肿瘤抑制物部分的恶性肿瘤部分则通过承受一定程度的AMPK活化作用经历了“糖分解转变”而减轻了底物限度。我认为对癌症发生产生作用的中间物代谢具有两面性关系；如果这一发现得到证明，那么它将对公众健康产生重要的深远意义，因为这一发现将支持预防肥胖、限制热量摄入和锻炼会减少易患癌症体质这一观点。