Liver cancer (LC) is a global health concern, marked by its high prevalence and mortality rates and known for its resistance to chemotherapy. The treatment of LC patients is facing great challenges. Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a LC marker that has been discovered in recent years, and there are sporadic data suggesting that it has an impact on the level of chemoresistance, but the exact mechanism remains to be deciphered. Our investigation, grounded in bioinformatics strategies including the TCGA database, GEO database, K-M plot database, GSEA, Pearson correlation analysis, and detection of clinical samples, led to the identification of TPX2 and its upstream transcription factor E2F8 as differentially expressed elements in LC tissues. We also probed the role of the axis in glycolysis, angiogenesis, tumor progression, and chemoresistance in LC cells. This was achieved by a battery of molecular and cellular experiments, such as qRT-PCR, CCK-8, Transwell, flow cytometry, and angiogenesis assays. Both TPX2 and E2F8 were upregulated in LC tissues and cells with E2F8 being responsible for the upregulation of TPX2. Through bioinformatics analysis, we observed a significant enrichment of TPX2 in the glycolysis and angiogenesis pathways. Cell-based experiments corroborated these findings, demonstrating that TPX2 knockdown led to significant inhibition of glycolysis and angiogenesis, along with a suppression of the malignant progression of LC cells. This was mirrored by a reduction in the IC50 values for cisplatin and apatinib to 0.8257 µM and 10.79 µM, respectively. In contrast, E2F8 overexpression reversed these effects in LC cells, increasing the IC50 values to 3.375 and 16.06 µM, respectively. The E2F8-TPX2 axis promotes glycolysis and angiogenesis in LC cells, which in turn accelerates cancer progression and reduces chemosensitivity.
Supplementary information: The online version contains supplementary material available at 10.1007/s10616-024-00655-w.
Keywords: Angiogenesis; Chemosensitivity; E2F8; Glycolysis; Liver cancer; TPX2.
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