Fig. 7: ZBTB10 is negatively correlated with PKLR expression.

A, B IHC staining of PKLR and ZBTB10 on consecutive sections of a PCa TMA (CA4) in two selected cases. Scale bars, 100 μm. C Correlation analysis of the intensities of PKLR and ZBTB10 of the PCa TMA (n = 49). PKLR expression was negatively associated with ZBTB10-expressing PCa samples. R, correlation coefficient; p, two-tailed p value. Significance was determined by correlation XY analyses in GraphPad Prism. D, E Tumor grade association analysis using a Chi-squared test of the CA9 PCa TMA. Intensities of PKLR (D) and ZBTB10 (E) staining were semiquantitatively scored using the H-index as follows: negative, weakly positive, moderately positive, and strongly positive. p values were calculated by a Chi-squared test performed using SPSS statistical 18.0 software. p < 0.001. F Proposed model for ADT-induced PKLR drives hormone-refractory PCa. Hormone-sensitive PCa activates AR signaling by increasing ZBTB10 leading to increased binding to the PKLR regulatory sequence and mediation of its transcriptional suppression. ADT induced inactivation of the AR-ZBTB10 pathway, leading to an abundance of PKLR through ZBTB10 loss of function. Overexpression of PKLR may upregulate glucose metabolism and NED progression of PCa cells. Targeting PKLR by potential PKLR inhibitors may reduce the PKLR-driven glycolysis and NED of ADT-resistant PCa.