title: Unraveling the mystery of cancer metabolism in the genesis of tumor-initiating cells and development of cancer.
abstract: 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.
authors.affiliation: Department of Bioinformatics, School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou, Jiangsu 215123, PR China.
authors.forename: Gaochuan
authors.initials: G
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Pengda
authors.initials: P
authors.lastname: Guo
authors.forename: Lucio
authors.initials: L
authors.lastname: Miele
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.forename: Quansheng
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008660:Metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010085:Oxidative Phosphorylation