p63 isoforms regulate metabolism of cancer stem cells

Matilde Todaro, Giorgio Stassi, Mirco Zucchelli, Antonella De Cola, Andrea Urbani, Daniela D'Agostino, Vincenzo De Laurenzi, Claudia Rossi, Simona D'Aguanno, Carmine Di Ilio, Claudio Cortese, Daniela Barcaroli, Domenico Ciavardelli

Risultato della ricerca: Articlepeer review

25 Citazioni (Scopus)

Abstract

p63 is an important regulator of epithelialdevelopment expressed in different variants containing (TA)or lacking (ΔN) the N-terminal transactivation domain. Thedifferent isoforms regulate stem-cell renewal and differentiationas well as cell senescence. Several studies indicatethat p63 isoforms also play a role in cancer development;however, very little is known about the role played by p63 inregulating the cancer stem phenotype. Here we investigate thecellular signals regulated by TAp63 and ΔNp63 in a model ofepithelial cancer stem cells. To this end, we used colon cancerstem cells, overexpressing either TAp63 or ΔNp63 isoforms,to carry out a proteomic study by chemical-labeling approachcoupled to network analysis. Our results indicate that p63 isimplicated in a wide range of biological processes, including metabolism. This was further investigated by a targeted strategy atboth protein and metabolite levels. The overall data show that TAp63 overexpressing cells are more glycolytic-active than ΔNp63cells, indicating that the two isoforms may regulate the key steps of glycolysis in an opposite manner. The mass-spectrometryproteomics 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.
Lingua originaleEnglish
pagine (da-a)2120-2136
Numero di pagine17
RivistaJournal of Proteome Research
Volume13
Stato di pubblicazionePublished - 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • ???subjectarea.asjc.1600.1600???

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