ArticleCell death & disease2023
TPX2 enhances the transcription factor activation of PXR and enhances the resistance of hepatocellular carcinoma cells to antitumor drugs.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Hypomethylation of the PXR gene promoter drives its overexpression in cisplatin-resistant EOC.Discover oncology · 2026Article
- In-silico analysis of multi-pathway crosstalk inhibition of santamarin in hepatocellular carcinoma.Journal of molecular histology · 2026Article
- TPX2-mediated autophagy maintains cancer stemness in LUAD: bioinformatic screening and functional validation.Frontiers in oncology · 2026Article
- Does consumption of a high-fructose diet during pregnancy and lactation exacerbate the effects of maternal exposure to cadmium on development and metabolic function of mouse offspring?Journal of toxicology and environmental health. Part A · 2026Article
- A Prognostic Risk Model for Hepatocellular Carcinoma Integrating Ferroptosis and Metabolic Reprogramming Signatures.Journal of Cancer · 2026Article
- Bile acid metabolism and hepatocellular carcinoma: mechanisms of drug resistance and intervention strategies.Precision clinical medicine · 2025Review
- Mechanisms and Therapeutic Advances of PXR in Metabolic Diseases and Cancer.International journal of molecular sciences · 2025Review
- Hepatocyte nuclear factor 4-Alpha: a key regulator in liver carcinogenesis.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Integrated Bioinformatic Analysis Reveals the Oncogenic, Survival, and Prognostic Characteristics of TPX2 in Hepatocellular Carcinoma.Biochemical genetics · 2025Article
- TPX2 promotes papillary renal cell carcinoma progression by forming a ceRNA with LINC00894.BMC medical genomics · 2025Article
- Essential oils from Amorpha fruticosa against hepatocellular carcinoma based on network pharmacology.BMC complementary medicine and therapies · 2025Article
- Identification of anoikis-related subtypes and a risk score prognosis model, the association with TME landscapes and therapeutic responses in hepatocellular carcinoma.Frontiers in immunology · 2025Article
- Deciphering the role of signal regulatory protein α in immunotherapy for solid tumors.Frontiers in immunology · 2025Review
- E2F8-TPX2 axis regulates glycolysis and angiogenesis to promote progression and reduce chemosensitivity of liver cancer.Cytotechnology · 2024Article
- Article
- Pralatrexate represses the resistance of HCC cells to molecular targeted agents via the miRNA-34a/Notch pathway.Discover oncology · 2024Article
- Enhancing antitumor activity of herceptin in HER2-positive breast cancer cells: a novel DNMT-1 inhibitor approach.Discover oncology · 2024Article
- A novel super-enhancer-related risk model for predicting prognosis and guiding personalized treatment in hepatocellular carcinoma.BMC cancer · 2024Article
- Article
- Pro-oncogene FBI-1 inhibits the ferroptosis of prostate carcinoma PC-3 cells via the microRNA-324-3p/GPX4 axis.Journal of Cancer · 2024Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pregnane X receptor (PXR) is an important regulator of hepatocellular carcinoma cellular resistance to antitumor drugs. Activation of PXR was modulated by the co-regulators. The target protein for the Xenopus plus end-directed kinesin-like protein (Xklp2) known as TPX2 that was previously considered as a tubulin regulator, also functions as the regulator of some transcription factors and pro-oncogenes in human malignances. However, the actions of TPX2 on PXR and HCC cells are still unclear. In the present study, our results demonstrate that the high expression of endogenous mRNA level of TPX2 not only correlated with the poor prognosis of advanced HCC patients who received sorafenib treatment but also with expression of PXR's downstream genes, cyp3a4 and/or mdr-1. Results from luciferase and real-time polymerase chain reaction (qPCR) showed that TPX2 leads to enhancement of the transcription factor activation of PXR. Protein-protein interactions between PXR and TPX2 were identified using co-immunoprecipitation. Mechanically, overexpression of TPX2 led to enhancement of PXR recruitment to its downstream gene cyp3a4's promoter region (the PXRE region) or enhancer region (the XREM region). Treatment of HCC cells with paclitaxel, a microtubule promoter, led to enhancement of the effects of TPX2, whereas vincristine, a microtubule depolymerizing agent caused a decrease in TPX2-associated effects. TPX2 was found to cause acceleration of the metabolism or clearance of sorafenib, a typical tyrosine kinase inhibitor (TKI) in HCC cells and in turn led to the resistance to sorafenib by HCC cells. By establishing novel actions of TXP2 on PXR in HCC cells, the results indicate that TPX2 could be considered a promising therapeutic target to enhance HCC cells sensitivity to antitumor drugs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.