Regulation of Mammary Stem Cell Quiescence via Post-Translational Modification of DeltaNp63alpha

This document is the annual summary report for the training grant awarded to Andrew DeCastro entitled Regulation of Mammary Stem Cell Quiescence via Post-Translational Modification of NP63alpha. Here, we report our findings under Task 3, as we have already completed our work on Tasks 1 and 2 in past years. Task 3 aims to determine the contribution of NP63alpha and NP63alpha-phosphorylation to therapeutic resistance in breast cancer stem cells. Based on or previous work, in which we show that TGF- mediates ALK5 dependent phosphorylation of NP63alpha, we also observed noticeable changes in cell phenotype indicative of EMT, a process utilized by cancer cells to mediate invasiveness, metastasis, chemoresistance and recurrence. As a result, we sought to determine the contribution of NP63alpha and its phosphorylation to the process of EMT and demonstrated that NP63alpha not only opposes TGF-beta induced EMT, but was sufficient to reverse a post-EMT breast cancer cell line back towards a more epithelial phenotype (MET). The data presented here identifies a role for NP63alpha as a potent oppose to TGF-beta mediated EMT. The original document contains color images.