KAT5 promotes tumor growth in androgen-independent prostate cancer by facilitating aerobic glycolysis.

This study aimed to explore the exact roles of lysine acetyltransferase 5 (KAT5) in prostate cancer (PCa). PCa tumour tissue samples and paired adjacent normal prostate tissues as well as three PCa cell lines were used. Gene expression was determined utilizing real-time PCR, western blotting and immunohistochemical staining. Cell viability, migration, and invasion was determined utilizing CCK-8, Transwell and Scratch assays, respectively. Levels of glucose, lactate, and ATP were measured utilizing corresponding assay kits. Extracellular acidification rate (ECAR) and oxygen consumption rates (OCR) were measured using Seahorse method. Xenografted tumor mice model was established to detect the roles of KAT5 in vivo. KAT5 expression was elevated in PCa tissue and cell lines, particularly in castration-resistant PCa tissue and DU145 cells. Overexpression of KAT5 promoted proliferation, migration, invasion, and expression of phosphorylated p38 and JNK of DU145 cells, whereas such effects was reversed after transfecting si-KAT5 or inhibiting p38 and JNK. KAT5 expression positively correlated with PKM and GLUT1, and its overexpression elevated PKM2 and GLUT1 levels. KAT5 overexpression promoted glucose uptake, lactate production, ATP levels in DU145 cells, and these were reversed after si-KAT5 treatment or inhibiting p38 and JNK. ECAR and OCR assays further confirmed that KAT5 facilitating aerobic glycolysis. After inhibiting glycolysis using 2-DG, KAT5 mediated cells proliferation was partly suppressed. Inhibition KAT5 expression suppressed tumor growth in vivo. KAT5 may involve in PCa tumor progression via p38-mediated aerobic glycolysis, which might be a promising anti-tumor strategy in PCa.