The Mechanism Of PKM2-COX-2 Axis In The Invasion And Migration Of Prostate Cancer Cells

BackgroundProstate cancer(PCa)is one of the leading causes of death in men around the world.Generally,the early localized prostate cancer patiens would accepte the surgery or radiontherapy at first and the same therapeutic strategy to the advanced prostare cancer patiens.Almost all of the prostate cancer patiens could achieve the good effect for sensitive to endocrine,but they resistance to the hormone treatment and occurrence of distal tissue metastasis at last.At that time,the patiens would die.Thus,the study on the mechanism of metastasis of prostate cancer treatment for rational drug design and prognosis,has important significance to further improve the level of treatment of prostate cancer.Pyruvate kinase(Pyruvate kinase 2)is one of the important rate limiting enzyme of glycolysis in tumor.PKM2 has overexpression in many tumors.It has been well know that PKM2 play an important role in metabolism in cytoplasm.PKM2 also has the non-metabolism function.Under the outside stimulation,PKM2 interacted with beta-catenin,HIF-1 and subsequently regulated tumor cell process.Cyclooxygenase 2(COX-2)is the rate-limiting enzyme in the synthesis of prostaglandins,which can promote the tumor progression,including tumor increasing proliferation,invasion,migration and inhibiting apoptosis.Especially the high expression of COX-2 leads to loss of E-cadherin and MMP-2 to promote tumor tissue invasion and metastasis.Whether or not PKM2 and COX-2 are involved in the invasion and migration of prostate cancer,the mechanism remains to exploredObjectivesThis study investigated the machinsm of PKM2 in migration and invasion of prostate cancer cells.MethodsPKM2 expression in the prostate cancer cells was changed by the plasimd,siRNA and lentivirus.In order to investigate the machinsm of PKM2 in migration and invasion of PCa cells,we used western bolt,real time PCR,co-IP and IF method.ResultsIn this study,we firstly confirmed that overexpress of PKM2 could promote the prostate cancer cells invasion and migration by transwell assay.On the contrary,knocking down the PKM2 inhibited the PCa cells migration and invasion.This results indicated that PKM2 promoted PCa cells migration and invasion.Then,we also found that COX-2 expression was reduce significant by real time PCR and western blot in the DU 145 and PC-3 stably knocking down PKM2.COX-2 expression significantly increased in the PCa cells which PKM2 were overexpression.That suggested PKM2 promoted COX-2 expression in PCa cells.Similary,we also found the p-ERK1/2 was inceased or decearesd by the PKM2 overexpression or knocking dowen in PCa cells.Indicateing PKM2 could promote the ERK1/2 phosphorylation in PCa cells.PKM2 interaction with ERK1/2 was confirmd by co-IP or IF.Inhibited the ERK1/2 could rescue the COX-2 expression and the PCa migration and invasion in the PKM2 overexpression.ConclusionPKM2 promotes the prostate cancer cells migration and invasion.That process might realize by mediateing COX-2 expression via ERK1/2 pathway.The research provided us a new horizon about the mechanism of invasion and metastasis in prostate cancer and new directions for prostate cancer treatment.