Fig. 7

Model. In enzalutamide-sensitive prostate cancers (LNCaP cells), ezalutamide treatment may activate the transcription factor GATA2 which functions as a CDC6 repressor, thereby stimulating cellular senescence at the expense of EMT. However, upon acquiring resistance to enzalutamide (C4-2B and PC-3 cells), prostate tumors exhibit an inverse regulation of the GATA2-CDC6 axis, leading to CDC6 stabilization via endogenous GATA2 downregulation, which activates EMT and abrogates senescence. Bypassing the GATA2-CDC6 axis by direct CDC6 depletion reverses oncogenic features and establishes senescence in enzalutamide-resistant cells, identifying CDC6 as a critical regulator of prostate cancer cell fate and response to therapy