Unraveling the mystery of cancer metabolism in the genesis of tumor-initiating cells and development of cancer.
Unraveling the mystery of cancer metabolism in the genesis of tumor-initiating cells and development of cancer.
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DOI：
10.1016/j.bbcan.2013.03.001
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发表时间：
2013-08
期刊：
影响因子：
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通讯作者：
Gaochuan Zhang;Ping Yang;P. Guo;L. Miele;F. Sarkar;Zhiwei Wang;Quansheng Zhou
中科院分区：
文献类型：
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作者：
Gaochuan Zhang;Ping Yang;P. Guo;L. Miele;F. Sarkar;Zhiwei Wang;Quansheng Zhou
强健的无氧代谢在肿瘤细胞的起源中起着致病作用，然而，在肿瘤起始细胞(TICS)发生中的致癌代谢基因、因子、途径和网络尚未被系统地总结。此外，TICS发生过程中的致癌代谢机制仍是个谜。在这篇综述中，我们讨论了多个癌症代谢相关基因(MRGs)，这些基因在抽动症中过度表达，并负责诱导多能干细胞。此外，我们还总结了致癌代谢基因和癌代谢物诱导代谢重编程，将正常的线粒体氧化磷酸化转换为癌症的无氧代谢，触发表观遗传、遗传和环境变化，驱动抽动的产生，促进癌症的发展。重要的是，癌症的新陈代谢受正负代谢调节因子的控制。积极的致癌代谢调节因子，包括关键致癌代谢基因、致癌代谢物、低氧和酸性环境，促进致癌代谢重编程和无氧代谢。然而，负性代谢调节因子的功能障碍，包括P53、PTEN和LKB1-AMPK-mTOR通路的缺陷，增强了癌症的新陈代谢。代谢平衡的丧失会导致致癌代谢重编程、痉挛的发生和肿瘤的发生。总而言之，这篇综述为这些致癌代谢在痉挛和肿瘤发生中的作用和机制提供了新的见解。因此，靶向关键致癌基因、肿瘤代谢物、通路、网络和酸性肿瘤微环境似乎是新的抗肿瘤治疗的一个有吸引力的策略。
Robust anaerobic metabolism plays a causative role in the origin of cancer cells; however, the oncogenic metabolic genes, factors, pathways, and networks in genesis of tumor-initiating cells (TICs) have not yet been systematically summarized. In addition, the mechanisms of oncogenic metabolism in the genesis of TICs are enigmatic. In this review, we discussed multiple cancer metabolism-related genes (MRGs) that are overexpressed in TICs and are responsible for inducing pluripotent stem cells. Moreover, we summarized that oncogenic metabolic genes and onco-metabolites induce metabolic reprogramming, which switches normal mitochondrial oxidative phosphorylation to cancer anaerobic metabolism, triggers epigenetic, genetic, and environmental alterations, drives the generation of TICs, and boosts the development of cancer. Importantly, cancer metabolism is controlled by positive and negative metabolic regulators. Positive oncogenic metabolic regulators, including key oncogenic metabolic genes, onco-metabolites, hypoxia, and an acidic environment, promote oncogenic metabolic reprogramming and anaerobic metabolism. However, dysfunction of negative metabolic regulators, including defects in p53, PTEN, and LKB1-AMPK-mTOR pathways, enhances cancer metabolism. Loss of the metabolic balance results in oncogenic metabolic reprogramming, genesis of TICs, and tumorigenesis. Collectively, this review provides new insight into the role and mechanism of these oncogenic metabolisms in the genesis of TICs and tumorigenesis. Accordingly, targeting key oncogenic genes, onco-metabolites, pathways, networks, and the acidic cancer microenvironment appears to be an attractive strategy for novel anti-tumor treatment.