p63 Isoforms Regulate Metabolism of Cancer Stem Cells

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.