title: Carbon source metabolism and its regulation in cancer cells.
abstract: Cancer cell proliferation and progression require sufficient supplies of nutrients including carbon sources, nitrogen sources, and molecular oxygen. Particularly, carbon sources and molecular oxygen are critical for the generation of ATP and building blocks, and for the maintenance of intracellular redox status. However, solid tumors frequently outgrow the blood supply, resulting in nutrient insufficiency. Accordingly, cancer cell metabolism shows aberrant biochemical features that are consequences of oncogenic signaling and adaptation. Those adaptive metabolism features, including the Warburg effect and addiction to glutamine, may form the biochemical basis for resistance to chemotherapy and radiation. A better understanding of the regulatory mechanisms that link the signaling pathways to adaptive metabolic reprogramming may identify novel biomarkers for drug development. In this review, we focus on the regulation of carbon source utilization at a cellular level, emphasizing its relevance to proliferative biosynthesis in cancer cells. We summarize the essential needs of proliferating cells and the metabolic features of glucose, lipids, and glutamine, and we review the roles of transcription regulators (i.e., HIF-1, c-Myc, and p53) and two major oncogenic signaling pathways (i.e., PI3K-Akt and MAPK) in regulating the utilization of carbon sources. Finally, the effects of glucose on cell proliferation and perspective from both biochemical and cellular angles are discussed.
authors.affiliation: Department of Biology, College of Arts and Sciences, Drexel University, Philadelphia, Pennsylvania, USA.
authors.forename: Chengqian
authors.initials: C
authors.lastname: Yin
authors.forename: Shuo
authors.initials: S
authors.lastname: Qie
authors.forename: Nianli
authors.initials: N
authors.lastname: Sang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D014408:Biomarkers, Tumor; D002244:Carbon / Q000378:metabolism*; D049109:Cell Proliferation; D004734:Energy Metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D051793:Hypoxia-Inducible Factor 1; D016271:Proto-Oncogene Proteins c-myc; D005973:Glutamine; D002244:Carbon; D000255:Adenosine Triphosphate; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; D009584:Nitrogen; D010100:Oxygen