title: p63 isoforms regulate metabolism of cancer stem cells.
abstract: p63 is an important regulator of epithelial development expressed in different variants containing (TA) or lacking (ΔN) the N-terminal transactivation domain. The different isoforms regulate stem-cell renewal and differentiation as well as cell senescence. Several studies indicate that p63 isoforms also play a role in cancer development; however, very little is known about the role played by p63 in regulating the cancer stem phenotype. Here we investigate the cellular signals regulated by TAp63 and ΔNp63 in a model of epithelial cancer stem cells. To this end, we used colon cancer stem cells, overexpressing either TAp63 or ΔNp63 isoforms, to carry out a proteomic study by chemical-labeling approach coupled to network analysis. Our results indicate that p63 is implicated in a wide range of biological processes, including metabolism. This was further investigated by a targeted strategy at both protein and metabolite levels. The overall data show that TAp63 overexpressing cells are more glycolytic-active than ΔNp63 cells, indicating that the two isoforms may regulate the key steps of glycolysis in an opposite manner. The mass-spectrometry proteomics data of the study have been deposited to the ProteomeXchange Consortium ( http://proteomecentral.proteomexchange.org ) via the PRIDE partner repository with data set identifiers PXD000769 and PXD000768.
authors.affiliation: Department of Experimental and Clinical Sciences, "G. d'Annunzio University" , Via dei Vestini 31, Chieti-Pescara 66100, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: D'Aguanno
authors.forename: Daniela
authors.initials: D
authors.lastname: Barcaroli
authors.forename: Claudia
authors.initials: C
authors.lastname: Rossi
authors.forename: Mirco
authors.initials: M
authors.lastname: Zucchelli
authors.forename: Domenico
authors.initials: D
authors.lastname: Ciavardelli
authors.forename: Claudio
authors.initials: C
authors.lastname: Cortese
authors.forename: Antonella
authors.initials: A
authors.lastname: De Cola
authors.forename: Silvia
authors.initials: S
authors.lastname: Volpe
authors.forename: Daniela
authors.initials: D
authors.lastname: D'Agostino
authors.forename: Matilde
authors.initials: M
authors.lastname: Todaro
authors.forename: Giorgio
authors.initials: G
authors.lastname: Stassi
authors.forename: Carmine
authors.initials: C
authors.lastname: Di Ilio
authors.forename: Andrea
authors.initials: A
authors.lastname: Urbani
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Laurenzi
mesh_terms: D006801:Humans; D007553:Isotope Labeling; D055432:Metabolomics; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000502:physiology; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D060066:Protein Interaction Maps / Q000502:physiology*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism*; D020543:Proteome / Q000032:analysis / Q000378:metabolism; D040901:Proteomics; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D020033:Protein Isoforms; D020543:Proteome; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins