ArticleInternational journal of cancer2009
The Karyopherin proteins, Crm1 and Karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation.
Article in International journal of cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02667873 (A Phase 1 Trial of SL-801, a Novel Inhibitor of XPO1 Nuclear Export, in Patients With Advanced Solid Tumors), which is not on this map. Cited by 143 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1 Trial of SL-801, a Novel Inhibitor of XPO1 Nuclear Export, in Patients With Advanced Solid Tumors
Who cites it
143 citing papers in PubMed, 247 citations in OpenAlex.
- Phase IB Study of Selinexor, a First-in-Class Inhibitor of Nuclear Export, in Patients With Advanced Refractory Bone or Soft Tissue Sarcoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016Trial
- Customizable host and viral transcript enrichment using CRISPR-Cas9 long-read sequencing for characterization of low-to-moderate abundance isoforms.NAR genomics and bioinformatics · 2026Article
- Cracking melanoma's armor: Supramolecular dual-strike on XPO1 and β-catenin to overcome resistance.Journal of advanced research · 2025Article
- Histone Deacetylase Inhibitors orchestrate epigenetic signalling and alter the nucleoporins and nuclear envelope in cervical cancer.Translational oncology · 2025Article
- Article
- Selinexor as a Therapeutic Target: Advances in Non-small Cell and Small Cell Lung Cancer Treatment Strategies.Recent patents on anti-cancer drug discovery · 2025Review
- Michael Acceptors as Anti-Cancer Compounds: Coincidence or Causality?International journal of molecular sciences · 2024Review
- Analysis of the effects of importin α1 on the nuclear translocation of IL-1α in HeLa cells.Scientific reports · 2024Article
- Nuclear localization signal-tagged systems: relevant nuclear import principles in the context of current therapeutic design.Chemical Society reviews · 2024Review
- Therapeutic targeting of nuclear export and import receptors in cancer and their potential in combination chemotherapy.IUBMB life · 2024Review
- Treatment of multiple myeloma with selinexor: a review.Therapeutic advances in hematology · 2024Review
- CRM1 expression: association with high prognostic value in laryngeal cancer.Turkish journal of medical sciences · 2023Article
- Proteomic Alteration in the Progression of Multiple Myeloma: A Comprehensive Review.Diagnostics (Basel, Switzerland) · 2023Review
- A general method for quantitative fractionation of mammalian cells.The Journal of cell biology · 2023Article
- A mass spectrometry-based approach for the identification of Kpnβ1 binding partners in cancer cells.Scientific reports · 2022Article
- KPNB1 modulates the Machado-Joseph disease protein ataxin-3 through activation of the mitochondrial protease CLPP.Cellular and molecular life sciences : CMLS · 2022Article
- P2RY2-AKT activation is a therapeutically actionable consequence of XPO1 inhibition in acute myeloid leukemia.Nature cancer · 2022Article
- Venetoclax enhances DNA damage induced by XPO1 inhibitors: A novel mechanism underlying the synergistic antileukaemic effect in acute myeloid leukaemia.Journal of cellular and molecular medicine · 2022Article
- Inhibitor of the Nuclear Transport Protein XPO1 Enhances the Anticancer Efficacy of KRAS G12C Inhibitors in Preclinical Models of KRAS G12C-Mutant Cancers.Cancer research communications · 2022Article
- mRNA-miRNA bipartite networks reconstruction in different tissues of bladder cancer based on gene co-expression network analysis.Scientific reports · 2022Article
83 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The Karyopherin proteins are involved in nucleo-cytoplasmic trafficking and are critical for protein and RNA subcellular localization. Recent studies suggest they are important in nuclear envelope component assembly, mitosis and replication. Since these are all critical cellular functions, alterations in the expression of the Karyopherins may have an impact on the biology of cancer cells. In this study, we examined the expression of the Karyopherins, Crm1, Karyopherin beta1 (Kpnbeta1) and Karyopherin alpha2 (Kpnalpha2), in cervical tissue and cell lines. The functional significance of these proteins to cancer cells was investigated using individual siRNAs to inhibit their expression. Microarrays, quantitative RT-PCR and immunofluorescence revealed significantly higher expression of Crm1, Kpnbeta1 and Kpnalpha2 in cervical cancer compared to normal tissue. Expression levels were similarly elevated in cervical cancer cell lines compared to normal cells, and in transformed epithelial and fibroblast cells. Inhibition of Crm1 and Kpnbeta1 in cancer cells significantly reduced cell proliferation, while Kpnalpha2 inhibition had no effect. Noncancer cells were unaffected by the inhibition of Crm1 and Kpnbeta1. The reduction in proliferation of cancer cells was associated with an increase in a subG1 population by cell cycle analysis and Caspase-3/7 assays revealed increased apoptosis. Crm1 and Kpnbeta1 siRNA-induced apoptosis was accompanied by an increase in the levels of growth inhibitory proteins, p53, p27, p21 and p18. Our results demonstrate that Crm1, Kpnbeta1 and Kpnalpha2 are overexpressed in cervical cancer and that inhibiting the expression of Crm1 and Kpnbeta1, not Kpnalpha2, induces cancer cell death, making Crm1 and Kpnbeta1 promising candidates as both biomarkers and potential anticancer therapeutic targets.
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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 OpenQuestion graph.