ArticleOncotarget2014
Selective inhibitors of nuclear export (SINE) as novel therapeutics for prostate cancer.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 63 citations in OpenAlex.
- A Phase II Trial of Selinexor, an Oral Selective Inhibitor of Nuclear Export Compound, in Abiraterone- and/or Enzalutamide-Refractory Metastatic Castration-Resistant Prostate Cancer.The oncologist · 2018Trial
- The XPO1 Inhibitor Eltanexor Modulates the Wnt/β-Catenin Signaling Pathway to Reduce Colorectal Cancer Tumorigenesis.Cancer research communications · 2025Article
- XPO1-dependency of DEK::NUP214 leukemia.Leukemia · 2025Article
- CRM1 regulates androgen receptor stability and impacts DNA repair pathways in prostate cancer, independent of the androgen receptor.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Label-free proteomic analysis of Duchenne and Becker muscular dystrophy showed decreased sarcomere proteins and increased ubiquitination-related proteins.Scientific reports · 2025Article
- Pharmacokinetic evaluation and bioavailability of KPT-335 (Verdinexor) in cats.Frontiers in veterinary science · 2025Article
- Identification of Novel Genes and Pathways of Ovarian Cancer Using a Comprehensive Bioinformatic Framework.Applied biochemistry and biotechnology · 2024Article
- The nuclear export protein exportin-1 in solid malignant tumours: From biology to clinical trials.Clinical and translational medicine · 2024Review
- The efficacy of selinexor (KPT-330), an XPO1 inhibitor, on non-hematologic cancers: a comprehensive review.Journal of cancer research and clinical oncology · 2023Review
- Azacitidine Is Synergistically Lethal with XPO1 Inhibitor Selinexor in Acute Myeloid Leukemia by Targeting XPO1/eIF4E/c-MYC Signaling.International journal of molecular sciences · 2023Article
- Nuclear Export Inhibitor KPT-8602 Synergizes with PARP Inhibitors in Escalating Apoptosis in Castration Resistant Cancer Cells.International journal of molecular sciences · 2021Article
- Exportins can inhibit major mitotic assembly eventsNucleus (Austin, Tex.) · 2020Article
- Melphalan and Exportin 1 Inhibitors Exert Synergistic Antitumor Effects in Preclinical Models of Human Multiple Myeloma.Cancer research · 2020Article
- Review
- NRG1/ERBB3 Pathway Activation Induces Acquired Resistance to XPO1 Inhibitors.Molecular cancer therapeutics · 2020Article
- The SINE Compound KPT-350 Blocks Dystrophic Pathologies in DMD Zebrafish and Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- PSPC1-interchanged interactions with PTK6 and β-catenin synergize oncogenic subcellular translocations and tumor progression.Nature communications · 2019Article
- Article
- Differential tissue expression of extracellular vesicle-derived proteins in prostate cancer.The Prostate · 2019Article
- Nuclear-Cytoplasmic Transport Is a Therapeutic Target in Myelofibrosis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Mislocalization of proteins is a common feature of cancer cells. Since localization of proteins is tightly linked to its function, cancer cells can inactivate function of a tumor suppressor protein through mislocalization. The nuclear exportin CRM1/XPO 1 is upregulated in many cancers. Targeting XPO 1 can lead to nuclear retention of cargo proteins such as p53, Foxo, and BRCA1 leading to cell cycle arrest and apoptosis. We demonstrate that selective inhibitors of nuclear export (SINE) can functionally inactivate XPO 1 in prostate cancer cells. Unlike the potent, but toxic, XPO 1 inhibitor leptomycin B, SINE inhibitors (KPT-185, KPT-330, and KPT-251) cause a decrease in XPO 1 protein level through the proteasomal pathway. Treatment of prostate cancer cells with SINE inhibitors lead to XPO 1 inhibition, as evaluated by RevGFP export assay, leading to nuclear retention of p53 and Foxo proteins, consequently, triggering apoptosis. Our data reveal that treatment with SINE inhibitors at nanomolar concentrations results in decrease in proliferation and colonogenic capacity of prostate cancer cells by triggering apoptosis without causing any cell cycle arrest. We further demonstrate that SINE inhibitors can be combined with other chemotherapeutics like doxorubicin to achieve enhanced growth inhibition of prostate cancer cells. Since SINE inhibitors offer increased bioavailability, reduced toxicity to normal cells, and are orally available they can serve as effective therapeutics against prostate cancer. In conclusion, our data reveals that nucleocytoplasmic transport in prostate cancer can be effectively targeted by SINE inhibitors.
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Registered trials
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.