Metabolic Regulation of Apoptosis in Cancer.
Apoptosis is a cellular suicide program that plays a critical role in development and human diseases, including cancer. Cancer cells evade apoptosis, thereby enabling excessive proliferation, survival under hypoxic conditions, and acquired resistance to therapeutic agents. Among various mechanisms that contribute to the evasion of apoptosis in cancer, metabolism is emerging as one of the key factors. Cellular metabolites can regulate functions of pro- and antiapoptotic proteins. In turn, p53, a regulator of apoptosis, also controls metabolism by limiting glycolysis and facilitating mitochondrial respiration. Consequently, with dysregulated metabolism and p53 inactivation, cancer cells are well-equipped to disable the apoptotic machinery. In this article, we review how cellular apoptosis is regulated and how metabolism can influence the signaling pathways leading to apoptosis, especially focusing on how glucose and lipid metabolism are altered in cancer cells and how these alterations can impact the apoptotic pathways.
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, United States.
K
K
Matsuura
Department of Molecular & Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States.
K
K
Canfield
Norris Cotton Cancer Center, Lebanon, NH, United States.
W
W
Feng
Department of Molecular & Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States; Norris Cotton Cancer Center, Lebanon, NH, United States. Electronic address: Manabu.Kurokawa@Dartmouth.edu.
M
M
Kurokawa
D000818:Animals; D017209:Apoptosis; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D050356:Lipid Metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction
D005947:Glucose
BCL-2 family; caspase; cell death; ceramide; glucose; hypoxia; lipids; p53
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