Fig. 5

High ING3 levels correlate with poor prognosis in prostate cancer patients. a Representative images of patient samples and their ING3 staining (red), pan-cytokeratin (PCK) (green), and DAPI (blue) that were classified as having high or low AR levels. The graph shows ING3 AQUA score in the patient subgroups based on their AR expression (Mann-Whitney test ***P < 0.001). b ING3 AQUA score in AR-low patient subgroup with various Gleason scores (ANOVA **P < 0.01). c, d Kaplan-Meier overall survival curves for AR-low subgroup of patients based on ING3 protein levels (c) or Gleason score (d) (log rank test). e Model of ING3 function in the AR pathway. ING3 serves as a scaffolding protein to coordinate interaction between members of TIP60 KAT complex with the AR complex in the cytoplasm. This promotes AR acetylation by TIP60, leading to nuclear translocation. Nuclear AR regulates gene expression promoting prostate cancer survival, proliferation, and migration. ING3 promotes AR recruitment to the FKBP5 ARE (and a subset of other genes containing AREs) and increases FKBP5 mRNA levels. This generates a positive feedback loop, making more FKBP5 available to bind AR, thereby stabilizing the complex, which promotes additional binding to ligand. Activation of this pathway promotes proliferation and migration of AR-responsive prostate cancer cells