American Chemical Society
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p63 Isoforms Regulate Metabolism of Cancer Stem Cells

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posted on 2014-04-04, 00:00 authored by Simona D’Aguanno, Daniela Barcaroli, Claudia Rossi, Mirco Zucchelli, Domenico Ciavardelli, Claudio Cortese, Antonella De Cola, Silvia Volpe, Daniela D’Agostino, Matilde Todaro, Giorgio Stassi, Carmine Di Ilio, Andrea Urbani, Vincenzo De Laurenzi
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 ( via the PRIDE partner repository with data set identifiers PXD000769 and PXD000768.