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.
|Number of pages||17|
|Journal||Journal of Proteome Research|
|Publication status||Published - 2014|
- General Chemistry