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Cell Death Dis
2023 Jan 27;141:64. doi: 10.1038/s41419-022-05537-7.
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TPX2 enhances the transcription factor activation of PXR and enhances the resistance of hepatocellular carcinoma cells to antitumor drugs.
Wang H
,
Chu F
,
Zhang XF
,
Zhang P
,
Li LX
,
Zhuang YL
,
Niu XF
,
He X
,
Li ZJ
,
Bai Y
,
Mao D
,
Liu ZW
,
Zhang DL
,
Li BA
.
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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.
Asteriti,
Cross-Talk between AURKA and Plk1 in Mitotic Entry and Spindle Assembly.
2015, Pubmed
Asteriti,
Cross-Talk between AURKA and Plk1 in Mitotic Entry and Spindle Assembly.
2015,
Pubmed
Banerjee,
Targeting xenobiotic receptors PXR and CAR in human diseases.
2015,
Pubmed
Byrnes,
Therapeutic regulation of autophagy in hepatic metabolism.
2022,
Pubmed
Chai,
Small-molecule modulators of PXR and CAR.
2016,
Pubmed
Chang,
The TPX2 gene is a promising diagnostic and therapeutic target for cervical cancer.
2012,
Pubmed
Chang,
GATA1 Promotes Gemcitabine Resistance in Pancreatic Cancer through Antiapoptotic Pathway.
2019,
Pubmed
Chen,
Megestrol acetate is a specific inducer of CYP3A4 mediated by human pregnane X receptor.
2021,
Pubmed
Chen,
LINE-1 ORF-1p enhances the transcription factor activity of pregnenolone X receptor and promotes sorafenib resistance in hepatocellular carcinoma cells.
2018,
Pubmed
Cheng,
Challenges of combination therapy with immune checkpoint inhibitors for hepatocellular carcinoma.
2020,
Pubmed
Cui,
MEIS1 functions as a potential AR negative regulator.
2014,
Pubmed
Douglas,
Nocodazole-Induced Expression and Phosphorylation of Anillin and Other Mitotic Proteins Are Decreased in DNA-Dependent Protein Kinase Catalytic Subunit-Deficient Cells and Rescued by Inhibition of the Anaphase-Promoting Complex/Cyclosome with proTAME but Not Apcin.
2020,
Pubmed
,
Xenbase
Feng,
Pregnane X receptor mediates sorafenib resistance in advanced hepatocellular carcinoma.
2018,
Pubmed
Feng,
Novel mTOR Inhibitor Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeting Agents.
2020,
Pubmed
Feng,
Which is the best combination of TACE and Sorafenib for advanced hepatocellular carcinoma treatment? A systematic review and network meta-analysis.
2018,
Pubmed
Foerster,
NAFLD-driven HCC: Safety and efficacy of current and emerging treatment options.
2022,
Pubmed
Gao,
ARQ-197 enhances the antitumor effect of sorafenib in hepatocellular carcinoma cells via decelerating its intracellular clearance.
2019,
Pubmed
Garrido,
Non-centrosomal TPX2-Dependent Regulation of the Aurora A Kinase: Functional Implications for Healthy and Pathological Cell Division.
2016,
Pubmed
Giubettini,
Control of Aurora-A stability through interaction with TPX2.
2011,
Pubmed
Guan,
WX-132-18B, a novel microtubule inhibitor, exhibits promising anti-tumor effects.
2017,
Pubmed
He,
New frontiers against sorafenib resistance in renal cell carcinoma: From molecular mechanisms to predictive biomarkers.
2021,
Pubmed
Huang,
Sorafenib derivatives-functionalized gold nanoparticles confer protection against tumor angiogenesis and proliferation via suppression of EGFR and VEGFR-2.
2021,
Pubmed
Ji,
Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis.
2019,
Pubmed
Jia,
Cimigenoside functions as a novel γ-secretase inhibitor and inhibits the proliferation or metastasis of human breast cancer cells by γ-secretase/Notch axis.
2021,
Pubmed
Jia,
Rhamnetin induces sensitization of hepatocellular carcinoma cells to a small molecular kinase inhibitor or chemotherapeutic agents.
2016,
Pubmed
Jia,
γ-Secretase inhibitors for breast cancer and hepatocellular carcinoma: From mechanism to treatment.
2021,
Pubmed
Jiang,
TPX2 regulates tumor growth in human cervical carcinoma cells.
2014,
Pubmed
,
Xenbase
Kadara,
Identification of gene signatures and molecular markers for human lung cancer prognosis using an in vitro lung carcinogenesis system.
2009,
Pubmed
Kavallaris,
Microtubules and resistance to tubulin-binding agents.
2010,
Pubmed
Koike,
TPX2 is a prognostic marker and promotes cell proliferation in neuroblastoma.
2022,
Pubmed
,
Xenbase
Leung,
EPHB2 Activates β-Catenin to Enhance Cancer Stem Cell Properties and Drive Sorafenib Resistance in Hepatocellular Carcinoma.
2021,
Pubmed
Li,
MicroRNA-140-3p enhances the sensitivity of hepatocellular carcinoma cells to sorafenib by targeting pregnenolone X receptor.
2018,
Pubmed
Li,
Rhamnetin decelerates the elimination and enhances the antitumor effect of the molecular-targeting agent sorafenib in hepatocellular carcinoma cells via the miR-148a/PXR axis.
2021,
Pubmed
Li,
Procaspase-3-activating compound 1 stabilizes hypoxia-inducible factor 1α and induces DNA damage by sequestering ferrous iron.
2018,
Pubmed
Li,
Effectiveness of TKI Inhibitors Combined With PD-1 in Patients With Postoperative Early Recurrence of HCC: A Real-World Study.
2022,
Pubmed
Liu,
A Novel Small Molecular Inhibitor of DNMT1 Enhances the Antitumor Effect of Radiofrequency Ablation in Lung Squamous Cell Carcinoma Cells.
2022,
Pubmed
Liu,
TPX2 as a novel prognostic biomarker for hepatocellular carcinoma.
2015,
Pubmed
,
Xenbase
Llovet,
Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma.
2021,
Pubmed
Lu,
LINE-1 ORF-1p functions as a novel androgen receptor co-activator and promotes the growth of human prostatic carcinoma cells.
2013,
Pubmed
Ma,
A Novel Small-Molecule Inhibitor of SREBP-1 Based on Natural Product Monomers Upregulates the Sensitivity of Lung Squamous Cell Carcinoma Cells to Antitumor Drugs.
2022,
Pubmed
Ma,
DNA methyltransferase mediates the hypermethylation of the microRNA 34a promoter and enhances the resistance of patient-derived pancreatic cancer cells to molecular targeting agents.
2020,
Pubmed
Ma,
TPX2 promotes cell proliferation and migration via PLK1 in OC.
2018,
Pubmed
,
Xenbase
Mani,
Activation of the steroid and xenobiotic receptor (human pregnane X receptor) by nontaxane microtubule-stabilizing agents.
2005,
Pubmed
Mohsenifar,
Prognostic values of proliferative markers ki-67 and repp86 in breast cancer.
2007,
Pubmed
Mu,
Long noncoding RNA NEAT1 aggravates sorafenib-resistance in non-small cell lung cancer via regulating miRNA-335/c-Met.
2021,
Pubmed
Nallani,
Induction of cytochrome P450 3A by paclitaxel in mice: pivotal role of the nuclear xenobiotic receptor, pregnane X receptor.
2003,
Pubmed
Oladimeji,
PXR: More Than Just a Master Xenobiotic Receptor.
2018,
Pubmed
Polverino,
The Aurora-A/TPX2 Axis Directs Spindle Orientation in Adherent Human Cells by Regulating NuMA and Microtubule Stability.
2021,
Pubmed
Robey,
Revisiting the role of ABC transporters in multidrug-resistant cancer.
2018,
Pubmed
Roskoski,
Properties of FDA-approved small molecule protein kinase inhibitors: A 2021 update.
2021,
Pubmed
Roskoski,
Properties of FDA-approved small molecule protein kinase inhibitors: A 2022 update.
2022,
Pubmed
Roskoski,
Properties of FDA-approved small molecule protein kinase inhibitors.
2019,
Pubmed
Roskoski,
Properties of FDA-approved small molecule protein kinase inhibitors: A 2020 update.
2020,
Pubmed
Shao,
ETS-1 induces Sorafenib-resistance in hepatocellular carcinoma cells via regulating transcription factor activity of PXR.
2018,
Pubmed
Shao,
miR-3609 Decelerates the Clearance of Sorafenib in Hepatocellular Carcinoma Cells by Targeting EPAS-1 and Reducing the Activation of the Pregnane X Receptor Pathway.
2020,
Pubmed
Shehu,
Targeting Xenobiotic Nuclear Receptors PXR and CAR to Prevent Cobicistat Hepatotoxicity.
2021,
Pubmed
Shigeishi,
Expression of TPX2 in salivary gland carcinomas.
2009,
Pubmed
Sun,
Target Protein for Xklp2 Functions as Coactivator of Androgen Receptor and Promotes the Proliferation of Prostate Carcinoma Cells.
2022,
Pubmed
,
Xenbase
Takahashi,
The AURKA/TPX2 axis drives colon tumorigenesis cooperatively with MYC.
2015,
Pubmed
Tang,
The mechanisms of sorafenib resistance in hepatocellular carcinoma: theoretical basis and therapeutic aspects.
2020,
Pubmed
Tian,
Molecular Mechanisms of Resistance to Tyrosine Kinase Inhibitors Associated with Hepatocellular Carcinoma.
2022,
Pubmed
Triarico,
Vincristine-Induced Peripheral Neuropathy (VIPN) in Pediatric Tumors: Mechanisms, Risk Factors, Strategies of Prevention and Treatment.
2021,
Pubmed
Vishnoi,
Ets1 mediates sorafenib resistance by regulating mitochondrial ROS pathway in hepatocellular carcinoma.
2022,
Pubmed
Wang,
Downregulation of TPX2 impairs the antitumor activity of CD8+ T cells in hepatocellular carcinoma.
2022,
Pubmed
Wang,
A novel small-molecule antagonist enhances the sensitivity of osteosarcoma to cabozantinib in vitro and in vivo by targeting DNMT-1 correlated with disease severity in human patients.
2021,
Pubmed
Wang,
Prognostic role of targeting protein for Xklp2 in solid tumors: A PRISMA-compliant systematic review and meta-analysis.
2018,
Pubmed
Warner,
Validation of TPX2 as a potential therapeutic target in pancreatic cancer cells.
2009,
Pubmed
Wei,
Epigenetic regulation of the DNMT1/MT1G/KLF4/CA9 axis synergises the anticancer effects of sorafenib in hepatocellular carcinoma.
2022,
Pubmed
Wei,
MiR-125b Loss Activated HIF1α/pAKT Loop, Leading to Transarterial Chemoembolization Resistance in Hepatocellular Carcinoma.
2021,
Pubmed
Xing,
PXR: a center of transcriptional regulation in cancer.
2020,
Pubmed
Xu,
Z-guggulsterone regulates MDR1 expression mainly through the pregnane X receptor-dependent manner in human brain microvessel endothelial cells.
2020,
Pubmed
Yang,
MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents.
2019,
Pubmed
Yang,
FBI-1 enhanced the resistance of triple-negative breast cancer cells to chemotherapeutic agents via the miR-30c/PXR axis.
2020,
Pubmed
Zhang,
Novel ADAM-17 inhibitor ZLDI-8 enhances the in vitro and in vivo chemotherapeutic effects of Sorafenib on hepatocellular carcinoma cells.
2018,
Pubmed
Zhang,
TPX2 mediates prostate cancer epithelial-mesenchymal transition through CDK1 regulated phosphorylation of ERK/GSK3β/SNAIL pathway.
2021,
Pubmed
Zhao,
Cross-talk between EPAS-1/HIF-2α and PXR signaling pathway regulates multi-drug resistance of stomach cancer cell.
2016,
Pubmed
Zhou,
TPX2 Enhanced the Activation of the HGF/ETS-1 Pathway and Increased the Invasion of Endocrine-Independent Prostate Carcinoma Cells.
2021,
Pubmed
Zhou,
Anlotinib enhances the antitumor activity of radiofrequency ablation on lung squamous cell carcinoma.
2021,
Pubmed
Zhu,
New knowledge of the mechanisms of sorafenib resistance in liver cancer.
2017,
Pubmed
