title: Phosphofructokinase: a mediator of glycolytic flux in cancer progression.
abstract: In view of the current limitations of cancer chemotherapy, there has been resurgent interest in re-visiting glycolysis to determine whether tumors could be killed by energy deprivation rather than solely by strategies to inhibit proliferation. Cancer cells exhibit a uniquely high rate of glucose utilization, converting it into lactate whose export subsequently creates an acidic extracellular environment that is thought to promote invasion and metastasis, in preference to its complete oxidation even in the presence of adequate oxygen supply. Reductive analysis of each step of glycolysis shows that, of the three rate limiting enzymes of the pathway, isoforms of phosphofructokinase may afford the greatest opportunity as targets to deprive cancer cells from essential energy and substrates for macromolecular synthesis for proliferation while allowing normal cells to survive. Strategies discussed include restricting the substrate for this enzyme. While prospects for monotherapy with glycolytic inhibitors are poor, combination therapy may be productive.
authors.affiliation: Faculty of Pharmacy, Kuwait University, PO Box 24923, Safat 13110, Kuwait. Electronic address: nada@hsc.edu.kw.
authors.forename: Nada
authors.initials: N
authors.lastname: Al Hasawi
authors.affiliation: Faculty of Pharmacy, Kuwait University, PO Box 24923, Safat 13110, Kuwait. Electronic address: maryoom45@gmail.com.
authors.forename: Mariam F
authors.initials: MF
authors.lastname: Alkandari
authors.affiliation: Faculty of Pharmacy, Kuwait University, PO Box 24923, Safat 13110, Kuwait. Electronic address: yunus@hsc.edu.kw.
authors.forename: Yunus A
authors.initials: YA
authors.lastname: Luqmani
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D018450:Disease Progression; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D025221:Phosphofructokinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D005947:Glucose; D008565:Membrane Proteins; D025221:Phosphofructokinases; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins
keywords: Aerobic glycolysis; Cancer; Fructose-1,6-bisphosphate; PFK