title: Key Players in Choline Metabolic Reprograming in Triple-Negative Breast Cancer.
abstract: Triple-negative breast cancer (TNBC), defined as lack of estrogen and progesterone receptors in the absence of protein overexpression/gene amplification of human epidermal growth factor receptor 2, is still a clinical challenge despite progress in breast cancer care.1H magnetic resonance spectroscopy allows identification and non-invasive monitoring of TNBC metabolic aberrations and elucidation of some key mechanisms underlying tumor progression. Thus, it has the potential to improvein vivodiagnosis and follow-up and also to identify new targets for treatment. Several studies have shown an altered phosphatidylcholine (PtdCho) metabolism in TNBCs, both in patients and in experimental models. Upregulation of choline kinase-alpha, an enzyme of the Kennedy pathway that phosphorylates free choline (Cho) to phosphocholine (PCho), is a major contributor to the increased PCho content detected in TNBCs. Phospholipase-mediated PtdCho headgroup hydrolysis also contributes to the build-up of a PCho pool in TNBC cells. The oncogene-driven PtdCho cycle appears to be fine tuned in TNBC cells in at least three ways: by modulating the choline import, by regulating the activity or expression of specific metabolic enzymes, and by contributing to the rewiring of the entire metabolic network. Thus, only by thoroughly dissecting these mechanisms, it will be possible to effectively translate this basic knowledge into further development and implementation of Cho-based imaging techniques and novel classes of therapeutics.
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: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Caramujo
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Cecchetti
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Spadaro
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità , Rome , Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Carpinelli
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
keywords: choline kinase; metabolic reprograming; phosphatidylcholine metabolism; phospholipase; triple-negative breast cancer