Mechanism of TPI-1 in Promoting the Proliferation and Invasion of Gastric Cancer Cells through Glycolytic Reprogramming

Haiwei WANG; Xiaohui ZHANG; Yunxiao TIAN; Shiqian WU

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Haiwei WANG, Xiaohui ZHANG, Yunxiao TIAN, Shiqian WU. Mechanism of TPI-1 in Promoting the Proliferation and Invasion of Gastric Cancer Cells through Glycolytic Reprogramming[J]. Journal of Kunming Medical University.

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Mechanism of TPI-1 in Promoting the Proliferation and Invasion of Gastric Cancer Cells through Glycolytic Reprogramming

Department of Pathology，Handan Central Hospital，Handan Hebei 056000，China

Received Date: 2025-07-17
Available Online: 2026-01-12

Abstract

Abstract

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: shNC, 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 shNC 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.
- TPI-1,
- HK2,
- Glycolysis,
- ECAR,
- Energy metabolism,
- Gastric cancer

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References(20)

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