PFKP Lactylation Promotes the Ovarian Cancer Progression Through Targeting PTEN.

Abstract

Ovarian cancer (OC) ranks among the most prevalent malignancies affecting females globally and is a leading cause of cancer-related mortality in women. This study sought to elucidate the influence of phosphofructokinase P (PFKP) on the progression of OC. A cohort of sixty OC patients was enrolled. OC cells were exposed to both normoxic and hypoxic conditions. Expression levels of PFKP and phosphatase and tensin homolog (PTEN) were quantified using real time quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses. Immunofluorescence confirmed these protein expression patterns. Glycolysis-related parameters, encompassing glucose uptake, extracellular lactate levels, extracellular acidification rates, and oxygen consumption rates, were assessed using commercially available kits. Lactylation status of PFKP was evaluated via immunoprecipitation followed by Western blot analysis. An OC xenograft mouse model was also established. Findings indicated elevated PFKP expression in OC tissues and cells. Additionally, PFKP knockdown attenuated glycolysis and counteracted the hypoxia-induced enhancement of glycolytic activity in OC cells. Mutation of the lysine (K) residue at position 392 diminished PFKP lactylation. Further investigations revealed that PFKP depletion upregulated PTEN expression in hypoxia-treated OC cells. Besides, PTEN suppression increased the glycolysis in hypoxia-treated OC cells. Animal study results demonstrated that PFKP inhibition curtailed OC tumor growth by modulating PTEN expression. Collectively, these results suggested that lactylation of PFKP at the K392 residue promoted glycolysis in OC cells by regulating PTEN, thereby facilitating the disease's progression.