title: Modulatory roles of glycolytic enzymes in cell death.
abstract: Cancer cells depend on an altered energy metabolism characterized by increased rates of both glycolysis and glutaminolysis. Accordingly, corresponding key metabolic enzymes are overexpressed or hyperactivated. As a result, this newly acquired metabolic profile determines most other cancer hallmarks including resistance to cell death. Recent findings highlighted metabolic enzymes as direct modulators of cell death pathways. Conversely, key mediators of cell death mechanisms are emerging as new binding partners of glycolytic actors; moreover, there is evidence that metabolic regulators re-localize to specific subcellular compartments or organelles to modulate various types of cell demise. The final outcome is the resistance against cell death programs. Current findings give a new meaning to metabolic pathways and allow understanding how they affect cancer-specific pathological alterations. Furthermore, they shed light on potentially targetable functions of metabolic actors to restore susceptibility of cancer cells to death. Here, we discuss an emerging interplay between cell metabolism and cell death, focusing on interactions that may offer new options of targeted therapies in cancer treatment involving more specifically hexokinases and glyceraldehyde-3-phosphate dehydrogenase.
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire de Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cerella
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire de Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg.
authors.forename: Mario
authors.initials: M
authors.lastname: Dicato
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: marcdiederich@snu.ac.kr.
authors.forename: Marc
authors.initials: M
authors.lastname: Diederich
mesh_terms: D016923:Cell Death / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology*; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000628:therapy
chemical_list: D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D006593:Hexokinase
keywords: Cancer; Cell death; GAPDH; Glycolysis; Hexokinase