Journal
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
Volume 1836, Issue 1, Pages 49-59Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbcan.2013.03.001
Keywords
Cancer metabolism; Stem cells; Cancer therapy; Oncogenic metabolic genes
Categories
Funding
- National Natural Science Foundation of China [30971138, 81172087]
- Chinese Academy of Science Special National Strategic Leader Project [XDA01040200]
- Suzhou City Scientific Research Funds [SWG0904, SS201004, SS201138]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Cultivation Base of State Key Laboratory of Stem Cell and Biomaterials built together by the Ministry of Science and Technology
- Jiangsu Province
- Jiangsu Province's Key Discipline of Medicine [XK201118]
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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. (C) 2013 Elsevier B.V. All rights reserved.
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