Abstract
Background: Among gastric cancer (GC) cases, stomach adenocarcinoma (STAD) comprises the majority, exceeding 95%. GC develops stealthily and quickly; the majority of cases are detected at advanced or mid-stage, which adversely affects the prognosis. Hence, delving into the molecular mechanisms contributing to GC advancement, and discovering innovative therapeutic targets and latent biomarkers for GC remain at the forefront of research. Methodology: QRT-PCR and western blot procedures were followed to make clear the targeting protein for Xklp2 (TPX2) expression in GC and surrounding non-tumor tissues. The impacts of TPX2 overproduction or attenuation on the biological traits of GC cells were examined through CCK-8 assay and transwell assay; meanwhile, vessel formation assays were employed to assess TPX2's impact on the vascular formation of GC. Furthermore, TCF/LEF activity was determined using the Top-Flash reporter plasmid; the production of proteins linked to epithelial-mesenchymal transition (EMT) and proteins linked to the Wnt/β-catenin pathway was evaluated through western blot. A nude mouse xenograft tumor model was established, and pathological staining was performed to detect tumor proliferation and angiogenesis. Results: TPX2 level was much higher in GC tissues and cells. When overexpressed, TPX2 contributed to these cells' viability, motility, infiltration, EMT, and angiogenesis, alongside activation of Wnt/β-catenin pathway; whereas, when silenced, TPX2 caused the opposite outcomes. Additionally, TPX2 overproduction enhanced the TCF/LEF transcriptional activity, while the introduction of a Wnt/β-catenin pathway inhibitor partly mitigated the GC advancement enhanced by overproducing TPX2. This phenomenon further confirms that TPX2 exerts carcinogenesis by enabling the Wnt/β-catenin pathway. Silencing TPX2 reduced tumor volume and weight in nude mice, inhibited angiogenesis and proliferation, and suppressed EMT in vivo. Conclusion: By activating the Wnt/β-catenin pathway, TPX2 promotes GC migration, invasion, and tumor angiogenesis, which collectively drive GC malignant progression.