p63 isoforms regulate metabolism of cancer stem cells

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

Research output: Contribution to journalArticlepeer-review

27 Citations (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.
Original languageEnglish
Pages (from-to)2120-2136
Number of pages17
JournalJournal of Proteome Research
Volume13
Publication statusPublished - 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • General Chemistry

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