Natter Klaus, Kohlwein Sepp D
University of Graz, Institute of Molecular Biosciences, Lipidomics Research Center Graz, Humboldtstrasse 50/II, 8010 Graz,
Biochim Biophys Acta. 2013 Feb;1831(2):314-26. doi: 10.1016/j.bbalip.2012.09.003. Epub 2012 Sep 16.
One of the paradigms in cancer pathogenesis is the requirement of a cell to undergo transformation from respiration to aerobic glycolysis - the Warburg effect - to become malignant. The demands of a rapidly proliferating cell for carbon metabolites for the synthesis of biomass, energy and redox equivalents, are fundamentally different from the requirements of a differentiated, quiescent cell, but it remains open whether this metabolic switch is a cause or a consequence of malignant transformation. One of the major requirements is the synthesis of lipids for membrane formation to allow for cell proliferation, cell cycle progression and cytokinesis. Enzymes involved in lipid metabolism were indeed found to play a major role in cancer cell proliferation, and most of these enzymes are conserved in the yeast, Saccharomyces cerevisiae. Most notably, cancer cell physiology and metabolic fluxes are very similar to those in the fermenting and rapidly proliferating yeast. Both types of cells display highly active pathways for the synthesis of fatty acids and their incorporation into complex lipids, and imbalances in synthesis or turnover of lipids affect growth and viability of both yeast and cancer cells. Thus, understanding lipid metabolism in S. cerevisiae during cell cycle progression and cell proliferation may complement recent efforts to understand the importance and fundamental regulatory mechanisms of these pathways in cancer.
癌症发病机制的一个范例是细胞需要从呼吸作用转变为有氧糖酵解（即瓦伯格效应）才能发生恶性转化。快速增殖的细胞对用于合成生物量、能量和氧化还原当量的碳代谢物的需求，与分化的静止细胞的需求有根本的不同，但这种代谢转换是恶性转化的原因还是结果仍不明确。其中一个主要需求是合成用于膜形成的脂质，以促进细胞增殖、细胞周期进程和胞质分裂。实际上，人们发现参与脂质代谢的酶在癌细胞增殖中起主要作用，而且这些酶中的大多数在酿酒酵母中是保守的。最值得注意的是，癌细胞生理学和代谢通量与发酵且快速增殖的酵母非常相似。这两种类型的细胞都具有用于脂肪酸合成及其掺入复合脂质的高度活跃途径，脂质合成或周转的失衡会影响酵母和癌细胞的生长及活力。因此，了解酿酒酵母在细胞周期进程和细胞增殖过程中的脂质代谢，可能会补充近期为理解这些途径在癌症中的重要性和基本调控机制所做的努力。
