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MATILDE TODARO

p63 isoforms regulate metabolism of cancer stem cells

  • Autori: D'Aguanno, S; Barcaroli, D; Rossi, C; Zucchelli, M; Ciavardelli, D; Cortese, C; De Cola, A; Volpe, S; D'Agostino, D; Todaro, M; STassi, G; Di Ilio, C; Urbani, C; De Laurenzi, V
  • Anno di pubblicazione: 2014
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • OA Link: http://hdl.handle.net/10447/100175

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.