PKCε-PKM2 Signalling Contributes To De Novo Lipogenesis And Tumor Growth Of Prostate Cancer

BackgroundProstate cancer is the second leading cause of death among men.One of the characteristics of tumor is abnormal metabolism,such as glucose metabolism,lipid metabolism and so on.Unlike the other tumors mainly through glucose metabolism to obtain energy,prostate cancer prefers to obtain energy through lipid metabolism.More than 90%of fatty acids in tumor cells are derived from de novo lipogenesis.De novo lipogenesis is closely related to tumor growth and metastasis.However,the mechanism of de novo lipogenesis regulating tumor growth and progression has not been fully understood.PKCε(Protein kinase Cε)is a subtype of the PKC(Protein kinase C)family and is closely associated with the growth and progression of a variety of tumors,including prostate cancer.Our previous study found that PKCε interacts with SMAD2/3 to promote the proliferation of prostate cancer cells.Recently,PKCε has been reported to contribute the progression of nonalcoholic fatty liver disease by regulating lipid metabolism.However,it is not clear whether PKCε regulates lipid metabolism in tumors and promotes tumor growth and progression by regulating lipid metabolism.PKM2 is a subtype of pyruvate kinase PK,an important rate-limiting enzyme for glycolysis.A lot of studies have confirmed that PKM2 in glucose metabolism is closely related to tumor growth and progression.Recent studies have shown that PKM2 also regulates lipid metabolism,but the upstream signaling molecules and their pathways involved in PKM2 metabolism remain unclear..In the present study,we demonstrate that PKCε interacts with PKM2 to promote phosphorylation of PKM2 and entry into nucleus,ultimately leading to de novo lipogenesis and tumor growth in prostate cancer.Research purpose and significance1.To investigate the role and molecular mechanism of PKCε in prostate cancer cells through PKM2 interaction to promote PKM2 nuclear translocation,thereby promoting de novo lipogenesis in prostate cancer cells and ultimately promoting prostate cancer growth.2.In vivo animal model were conducted to investigate that PKCε mediates de novo lipogenesis and promotes prostate cancer growth through PKM2.In the present study,we demonstrate that interaction of PKCε with PKM2 contributes to the tumor growth through promoting de novo lipogenesis,thus providing a new potential target for targeted therapy-strategies for metabolic abnormalities in prostate cancer.Research content and methodsIn this study,we investigated the effect of PKCε on de novo lipogenesis of prostate cancer cells by overexpressing lentivirus,siRNA gene silencing,and overexpressing plasmids strategies.Then,immunofluorescence staining,co-immunoprecipitation,Western Blot and other experimental techniques confirmed that PKCε promotes PKM2 nuclear translocation by interacting with PKM2.Finally,in vitro and in vivo experiments confirmed that the PKCε-PKM2 signalling promotes the growth and proliferation of prostate cancer by regulating de novo lipogenesis.Research results1.The expression of PKCε promotes de novo lipogenesis in prostate cancer cells;2.PKCε promotes the expression of key enzymes related to de novo lipogenesis in prostate cancer cells;3.PKCε interacts with PKM2 promotes the phosphorylation of PKM2 at Ser37 and PKM2 nuclear translocation.4.In vitro experiments confirmed that PKCε mediates de novo lipogenesis and promotes the growth of prostate cancer cells;5.Animal experiments have confirmed that PKCε promotes the growth of prostate cancer through PKM2-mediated de novo lipogenesis.ConclusionsIn summary,PKCε interacts with PKM2 to promote phosphorylation of PKM2 at Ser37,promoting nuclear translocation of PKM2,thereby promoting de novo lipogenesis in prostate cancer,and ultimately promoting prostate cancer growth.This study laid a foundation for further exploration of the relationship between lipid metabolism and tumor growth,and provided a new target for the diagnosis and treatment of prostate cancer.