PDF(Pubmed)
Abstract：
The atavistic theory of cancer posits that cancer emerges and progresses through the reversion of cellular phenotypes to more ancestral types with genomic and epigenetic changes deactivating recently evolved genetic modules and activating ancient survival mechanisms. This theory aims at explaining the known cancer hallmarks and the paradox of cancer\'s predictable progression despite the randomness of genetic mutations. Lineweaver and colleagues recently proposed the Serial Atavism Model (SAM), an enhanced version of the atavistic theory, which suggests that cancer progression involves multiple atavistic reversions where cells regress through evolutionary stages, losing recently evolved traits first and reactivating primitive ones later. The Warburg effect, where cancer cells upregulate glycolysis and lactate production in the presence of oxygen instead of using oxidative phosphorylation, is one of the key feature of the SAM. It is associated with the metabolism of ancient cells living on Earth before the oxygenation of the atmosphere. This review addresses the question of whether cancer metabolism can be considered as an atavistic reversion. By analyzing several known characteristics of cancer metabolism, we reach the conclusion that this version of the atavistic theory does not provide an adequate conceptual frame for cancer research. Cancer metabolism spans a whole spectrum of metabolic states which cannot be fully explained by a sequential reversion to an ancient state. Moreover, we interrogate the nature of cancer metabolism and discuss its characteristics within the framework of the SAM.
摘要：
癌症的返祖理论认为，癌症的出现和发展是通过细胞表型向更多祖先类型的回归，基因组和表观遗传变化使最近进化的遗传模块失活并激活古老的生存机制。这一理论旨在解释已知的癌症标志和癌症的可预测进展的悖论，尽管基因突变的随机性。Lineweaver和他的同事最近提出了序列交叉主义模型(SAM)，返世论的增强版，这表明癌症的进展涉及多个返祖逆转，其中细胞在进化阶段退化，首先失去最近进化的特征，然后重新激活原始特征。Warburg效应,癌细胞在氧气存在下上调糖酵解和乳酸生成，而不是使用氧化磷酸化，是SAM的关键功能之一。它与大气氧合之前生活在地球上的古代细胞的新陈代谢有关。这篇综述解决了癌症代谢是否可以被视为返转的问题。通过分析癌症代谢的几个已知特征，我们得出的结论是,这个版本的返祖理论没有为癌症研究提供足够的概念框架.癌症代谢跨越了代谢状态的整个范围，这不能通过顺序恢复到古代状态来完全解释。此外，我们询问癌症代谢的性质，并在SAM框架内讨论其特征。
