Collaboration of Kras and Androgen receptor signaling stimulates EZH2 expression and tumor propagating cells in prostate cancer
Menée à l'aide d'un modèle murin, cette étude met en évidence un mécanisme par lequel, en activant l'expression du facteur régulateur de la chromatine EZH2, le gène Kras et le récepteur des androgènes favorisent la progression d'un cancer de la prostate
Elevation of the chromatin repression factor EZH2 is associated with progression and poor prognosis in several human cancers, including prostate cancer. However, the mechanisms driving EZH2 expression are not fully understood. In this study, we investigated the functional synergy in prostate cancers in mice resulting from activation of the androgen receptor (AR), Kras and Akt, which drive three of the most frequently activated oncogenic signaling pathways in prostate cancer. While any two of these three events were sufficient to promote the formation and progression of prostate cancer, only the synergy of AR and Kras signaling could elevate EZH2 expression and expand prostate cancer progenitor cells in vivo. Our findings have revealed a genetic mechanism resulting in enhanced EZH2 expression during the progression of aggressive prostate cancer, with important implications for understanding how to target advanced disease where cancer progenitor cells may be critical.