Role of TPX2 in glycolytic activity and malignant progression of colorectal cancer

Metabolic reprogramming, particularly enhanced glycolysis, is a hallmark of colorectal cancer (CRC) progression. Although TPX2 is an oncogene implicated in multiple cancers, its role in regulating glycolysis in CRC remains unclear. Differentially expressed genes in CRC were identified using GEO datasets, followed by functional enrichment analysis and protein–protein interaction (PPI) network construction to screen key candidates. TPX2 was identified as a hub gene and selected for further experimental validation. TPX2 expression was further validated using TIMER2.0 and GEPIA2 databases. In CRC cell lines, TPX2 was silenced, and effects on cell viability, migration, invasion, and glycolysis were assessed using CCK-8 assays, extracellular acidification rate (ECAR) analysis, glucose uptake, and lactate production assays. Rescue experiments were performed using the PKM2 activator DASA-58 to explore the potential involvement. TPX2 was identified as a hub gene and was significantly upregulated in CRC tissues and cell lines ( P < 0.05). TPX2 knockdown markedly inhibited CRC cell viability, migration, and invasion. Meanwhile, glycolytic activity was suppressed, as evidenced by reduced ECAR, glucose consumption, and lactate production. In addition, expression levels of PKM2, GLUT1, and LDHA were significantly decreased ( P < 0.05). Notably, pharmacological activation of PKM2 by DASA-58 partially reversed the inhibitory effects of TPX2 silencing on glycolysis and malignant phenotypes. TPX2 silencing suppresses CRC cell viability, migration, invasion, and glycolytic activity. The partial reversal of these effects by pharmacological activation of PKM2 suggests that PKM2-associated glycolytic metabolism may contribute, at least in part, to the observed effects of TPX2 silencing. However, the precise molecular relationship between TPX2 and PKM2 remains unclear. These findings support further investigation of the association between TPX2, glycolytic metabolism, and CRC progression.