title: Choline Metabolism Alteration: A Focus on Ovarian Cancer.
abstract: Compared with normal differentiated cells, cancer cells require a metabolic reprograming to support their high proliferation rates and survival. Aberrant choline metabolism is a fairly new metabolic hallmark reflecting the complex reciprocal interactions between oncogenic signaling and cellular metabolism. Alterations of the involved metabolic network may be sustained by changes in activity of several choline transporters as well as of enzymes such as choline kinase-alpha (ChoK-α) and phosphatidylcholine-specific phospholipases C and D. Of note, the net outcome of these enzymatic alterations is an increase of phosphocholine and total choline-containing compounds, a "cholinic phenotype" that can be monitored in cancer by magnetic resonance spectroscopy. This review will highlight the molecular basis for targeting this pathway in epithelial ovarian cancer (EOC), a highly heterogeneous and lethal malignancy characterized by late diagnosis, frequent relapse, and development of chemoresistance. Modulation of ChoK-α expression impairs only EOC but not normal ovarian cells, thus supporting the hypothesis that "cholinic phenotype" is a peculiar feature of transformed cells and indicating ChoK-α targeting as a novel approach to improve efficacy of standard EOC chemotherapeutic treatments.
authors.affiliation: Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Bagnoli
authors.affiliation: Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Granata
authors.affiliation: Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Nicoletti
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research, In Vivo Cellular and Molecular Imaging Center, The Johns Hopkins University School of Medicine , Baltimore, MD , USA.
authors.forename: Balaji
authors.initials: B
authors.lastname: Krishnamachary
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research, In Vivo Cellular and Molecular Imaging Center, The Johns Hopkins University School of Medicine , Baltimore, MD , USA.
authors.forename: Zaver M
authors.initials: ZM
authors.lastname: Bhujwalla
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Canese
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Podo
authors.affiliation: Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Functional Genomics and Informatics, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Canevari
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Egidio
authors.initials: E
authors.lastname: Iorio
authors.affiliation: Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy.
authors.forename: Delia
authors.initials: D
authors.lastname: Mezzanzanica
keywords: antioxidant defense; choline kinase; ovarian cancer; phosphocholine metabolism; reversal of drug resistance