title: PTEN deficiency and mutant p53 confer glucose-addiction to thyroid cancer cells: impact of glucose depletion on cell proliferation, cell survival, autophagy and cell migration.
abstract: Proliferating cancer cells oxidize glucose through the glycolytic pathway. Since this metabolism is less profitable in terms of ATP production, cancer cells consume large quantity of glucose, and those that experience insufficient blood supply become glucose-addicted. We have analyzed the response to glucose depletion in WRO and FTC133 follicular thyroid cancer cells, which differ in the expression of two key regulators of the glucose metabolism. WRO cells, which express wild type p53 and PTEN, showed a higher rate of cell proliferation and were much less sensitive to glucose-depletion than FTC133 cells, which are PTEN null and express mutant p53. Glucose depletion slowed-down the autophagy flux in FTC133 cells, not in WRO cells. In a wound-healing assay, WRO cells were shown to migrate faster than FTC133 cells. Glucose depletion slowed down the cell migration rate, and these effects were more evident in FTC133 cells. Genetic silencing of either wild-type PTEN or p53 in WRO cells resulted in increased uptake of glucose, whereas the ectopic expression of PTEN in FTC133 cells resulted in diminished glucose uptake. In conclusion, compared to WRO, FTC133 cells were higher glucose up-taker and consumer. These data do not support the general contention that cancer cells lacking PTEN or expressing the mutant p53R273H are more aggressive and prone to better face glucose depletion. We propose that concurrent PTEN deficiency and mutant p53 leads to a glucose-addiction state that renders the cancer cell more sensitive to glucose restriction. The present observation substantiates the view that glucose-restriction may be an adjuvant strategy to combat these tumours.
authors.affiliation: Laboratory of Molecular Pathology, Department of Health Sciences, Università del Piemonte Orientale "A. Avogadro", Novara (Italy).
authors.forename: Federica
authors.initials: F
authors.lastname: Morani
authors.affiliation: Laboratory of Molecular Pathology, Department of Health Sciences, Università del Piemonte Orientale "A. Avogadro", Novara (Italy).
authors.forename: Suratchanee
authors.initials: S
authors.lastname: Phadngam
authors.affiliation: Laboratory of Molecular Pathology, Department of Health Sciences, Università del Piemonte Orientale "A. Avogadro", Novara (Italy).
authors.forename: Carlo
authors.initials: C
authors.lastname: Follo
authors.affiliation: Laboratory of Molecular Pathology, Department of Health Sciences, Università del Piemonte Orientale "A. Avogadro", Novara (Italy).
authors.forename: Rossella
authors.initials: R
authors.lastname: Titone
authors.affiliation: Laboratory of Molecular Pathology, Department of Health Sciences, Università del Piemonte Orientale "A. Avogadro", Novara (Italy) ; Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Visa
authors.initials: V
authors.lastname: Thongrakard
authors.affiliation: Unit of Oncology, Department of Translational Medicine, Università del Piemonte Orientale "A. Avogadro", Novara (Italy).
authors.forename: Alessandra
authors.initials: A
authors.lastname: Galetto
authors.affiliation: Unit of Oncology, Department of Translational Medicine, Università del Piemonte Orientale "A. Avogadro", Novara (Italy).
authors.forename: Oscar
authors.initials: O
authors.lastname: Alabiso
authors.affiliation: Laboratory of Molecular Pathology, Department of Health Sciences, Università del Piemonte Orientale "A. Avogadro", Novara (Italy).
authors.forename: Ciro
authors.initials: C
authors.lastname: Isidoro
keywords: PTEN; Warburg effect; autophagy; glucose; metabolic stress; p53