Evolution of Tumor Metabolism might Reflect Carcinogenesis as a Reverse Evolution process (Dismantling of Multicellularity).
Evolution of Tumor Metabolism might Reflect Carcinogenesis as a Reverse Evolution process (Dismantling of Multicellularity).
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DOI：
10.3390/cancers3033002
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发表时间：
2011-07-22
期刊：
影响因子：
5.2
通讯作者：
Bashir AH
中科院分区：
文献类型：
--
作者：
Alfarouk KO;Shayoub ME;Muddathir AK;Elhassan GO;Bashir AH
癌变是通过一系列步骤发生的，从正常到良性，最后是恶性表型。伴随着这一癌症进化轨迹的是类似的代谢转变，从正常代谢到巴斯德和/或克拉布里效应，再到华宝效应，最后是同类相食和/或乳酸共生。由于乳酸作为糖酵解的最终产物产生，肿瘤克隆获得了依赖乳酸作为能量燃料的新表型。Warburg效应的存在表明，一些肿瘤细胞经历了部分(如果不是完全的)去内共生，因此癌细胞已经成为单细胞微生物(反Dollo定律)，特别是当它们进化到以食人为代谢方式时，而依赖乳酸作为其能量燃料的氧化类型的细胞可能代表外内共生。因此，最终可以认为该肿瘤菌落是一个完整的代谢生态系统。对肿瘤代谢的正确认识将有助于在常规化疗之外发现潜在的抗癌药物。
Carcinogenesis occurs through a series of steps from normal into benign and finally malignant phenotype. This cancer evolutionary trajectory has been accompanied by similar metabolic transformation from normal metabolism into Pasteur and/or Crabtree-Effects into Warburg-Effect and finally Cannibalism and/or Lactate-Symbiosis. Due to lactate production as an end-product of glycolysis, tumor colonies acquire new phenotypes that rely on lactate as energetic fuel. Presence of Warburg-Effect indicates that some tumor cells undergo partial (if not complete) de-endosymbiosis and so cancer cells have been become unicellular microorganism (anti-Dollo's Law) specially when they evolve to develop cannibalism as way of metabolism while oxidative types of cells that rely on lactate, as their energetic fuel, might represent extra-endosymbiosis. Thus, at the end, the cancer colony could be considered as integrated metabolic ecosystem. Proper understanding of tumor metabolism will contribute to discover potential anticancer agents besides conventional chemotherapy.