Molecular Mechanisms Of Glycine Decarboxylase (GLDC) Mediating Metastasis Of Prostate Cancer By Enhancing Warburg Effect

ObjectiveMetastasis of prostate cancer is one of the main causes of refractory prostate cancer and death.Early and accurate prediction and blocking of metastasis signaling pathway is a difficult and hot topic in prostate cancer research,which has great clinical significance and value.The imbalance between tumor metastasis promoting and inhibiting factors is the main cause of cancer metastasis.The initiation of the specific energy metabolism pattern(Warburg effect)of cancer cells and a series of effects(cell metabolism,activation of metastasis promoting genes,etc.)play an important role in breaking this balance.Glycine decarboxylase(GLDC)is closely related to Warburg effect.However,its specific mechanism needs to be clarified.Therefore,we will explore the relationship between GLDC and Warburg effect and the molecular mechanism of GLDC mediating prostate cancer metastasis.Method1.TCGA database was used to analyze the expression level of GLDC in normal prostate tissue and prostate cancer tissue.Western Blot assay was used to verify the expression of GLDC in prostate cancer cells and tissues.2.After differentially expressed GLDC,cell scratch test,Transwell migration and invasion test were used to detect the parallel migration,vertical migration and invasion ability of prostate cancer cells3.After differentially expressed GLDC,metabolomic microarray was used to analyze the metabolic changes of prostate cancer cells.Glucose uptake,lactate production and lactate dehydrogenase activity of prostate cancer cells were measured by glucose uptake test,lactate production test and lactate dehydrogenase test.4.After transfection of wild-type GLDC overexpression plasmid and point mutation inactivated GLDC plasmid into 22RV1 cells,the ability of parallel migration,vertical migration and invasion were tested by scratch test,Transwell migration and invasion test.Glucose uptake,lactate production and lactate dehydrogenase activity were measured by glucose uptake,lactate production and lactate dehydrogenase activity.5.Clinical significance of GLDC in prostate cancer:univariate and multivariate analysis and survival analysis.Result1.The expression of GLDC in normal prostate tissue was significantly lower than that in prostate cancer tissue.The expression of GLDC in localized prostate cancer cells(22RV1)and metastatic prostate cancer cells(DU145,LnCaP)increased in turn.2.Silence or overexpression of GLDC can significantly reduce or improve the parallel migration,vertical migration and invasive ability of prostate cancer cells.3.Metabolomic microarray analysis showed that differential expression of GLDC could significantly change the metabolic level of prostate cancer cells.Silence or overexpression of GLDC can significantly reduce or increase glucose uptake,lactate production and lactate dehydrogenase activity in prostate cancer cells.4.22RV1 cells successfully overexpressed wild-type GLDC overexpression plasmid and point mutation enzyme inactivated GLDC plasmid respectively.Compared with 22RV1 cells inactivated by GLDC point mutation enzyme,the parallel migration,vertical migration and invasion ability of 22RV1 cells overexpressed by wild-type GLDC were significantly improved,and the glucose uptake,lactate production and lactate dehydrogenase activity were also significantly increased.5.Univariate and multivariate analysis showed that high expression of GLDC was an independent risk factor for clinical progression of prostate cancer.The analysis of progression-free survival showed that the progression-free survival rate of prostate cancer patients with high GLDC expression was significantly reduced.Conclusion1.GLDC is highly expressed in prostate cancer tissues and metastatic prostate cancer cells.2.GLDC can promote invasion and metastasis of prostate cancer.3.GLDC mediates invasion and metastasis of prostate cancer by enhancing Warburg effect.4.The activity of GLDC is essential for the invasion and metastasis of prostate cancer cells.5.The high expression of GLDC is closely related to the clinical progression and prognosis of prostate cancer.