The awakening of an advanced malignant cancer: an insult to the mitochondrial genome.
The awakening of an advanced malignant cancer: an insult to the mitochondrial genome.
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DOI：
10.1016/j.bbagen.2011.08.017
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发表时间：
2012-05
影响因子：
3
通讯作者：
Higuchi, Masahiro
中科院分区：
文献类型：
--
作者：
Cook, Cody C.;Higuchi, Masahiro
只需数月至数年，原发性癌症即可进展为晚期表型，即发生转移并对临床治疗产生耐药性。早在 1900 年代，人们就发现癌症发展到晚期表型通常与疾病的代谢特征从呼吸状态转变为厌氧发酵状态有关，这种现象被称为瓦伯格效应。文献中的报告强烈表明，瓦伯格效应是对癌症内线粒体基因组内容的序列和/或拷贝数完整性丧失的反应而产生的。关于癌症进展的多项研究表明，线粒体基因组内容的突变和/或拷贝数变化可以支持癌症的早期发展，直到；突变负荷和/或线粒体基因组内容拷贝数的减少至耗尽诱导疾病进展至晚期表型。总的来说，有证据表明，人类细胞已将线粒体基因组内容整合到一种细胞机制中，当病理驱动时，可以将癌症从起源的亲本组织去分化（不分化）成一种自主疾病，破坏人体的层次结构和功能。
In only months-to-years a primary cancer can progress to an advanced phenotype that is metastatic and resistant to clinical treatments. As early as the 1900s, it was discovered that the progression of a cancer to the advanced phenotype is often associated with a shift in the metabolic profile of the disease from a state of respiration to anaerobic fermentation – a phenomenon denoted as the Warburg Effect. Reports in the literature strongly suggest that the Warburg Effect is generated as a response to a loss in the integrity of the sequence and/or copy number of the mitochondrial genome content within a cancer. Multiple studies regarding the progression of cancer indicate that mutation, and/or, a flux in the copy number, of the mitochondrial genome content can support the early development of a cancer, until; the mutational load and/or the reduction-to-depletion of the copy number of the mitochondrial genome content induces the progression of the disease to an advanced phenotype. Collectively, evidence has revealed that the human cell has incorporated the mitochondrial genome content into a cellular mechanism that, when pathologically actuated, can de (un)differentiate a cancer from the parental tissue of origin into an autonomous disease that disrupts the hierarchical structure-and-function of the human body.
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