TPI-1通过糖酵解重编程促进胃癌细胞增殖和侵袭的机制OA

Objective To investigate the potential mechanism of TPI-1 intervention in gastric cancer progression from the perspective of glycolytic reprogramming.Methods TPI-1 knockdown and overexpression gastric cancer cell models were constructed.Experimental cells were divided into four groups:shCtrl,shTPI-1,oe-Ctrl,and oe-TPI-1.Cell viability was detected using the CCK-8 assay;invasive capacity was assessed using the Transwell assay;glycolytic capacity was measured using glycolytic stress test to detect ECAR reflecting the glycolytic capacity of different groups of gastric cancer cells;Western blot was used to analyze the expression levels of apoptosis-related,invasion-related,and glycolysis-related characteristic markers in different groups;immunofluorescence and co-IP experiments were performed to verify the colocalization and binding relationship between TPI-1 and HK2.Results Compared with the shCtrl group,the shTPI-1 group showed reduced cell proliferation and invasion capacity(P<0.01);compared with the oe-Ctrl group,the oe-TPI-1 group demonstrated enhanced proliferation and invasion capacity(P<0.01);after TPI-1 knockdown,both basal glycolytic capacity and maximum glycolytic capacity were decreased(P<0.01);in the shTPI-1 group,protein levels of glycolytic key enzymes HK2 and PKM2 were significantly reduced(P<0.01),and MMP-2,MMP-9,N-cadherin,Bcl-2,and COX4I1 were significantly downregulated(P<0.01),while NOX4,E-cadherin,Bax,and cleaved caspase-3 were significantly upregulated(P<0.01);the oe-TPI-1 group showed opposite trends;immunofluorescence analysis revealed colocalization of TPI-1 and HK2 within cells;co-immunoprecipitation preliminarily confirmed that TPI-1 and HK2 may interact.Conclusion TPI-1 promotes gastric cancer progression by interacting with HK2,continuously activating the initiation step of glycolysis,and promoting glycolysis reprogramming.