posted on 2014-04-04, 00:00authored bySimona 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 (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository with data set identifiers PXD000769
and PXD000768.