ArticlemBio2019
CRISPR-Cas9 Screening of Kaposi's Sarcoma-Associated Herpesvirus-Transformed Cells Identifies XPO1 as a Vulnerable Target of Cancer Cells.
Article in mBio, 2019. 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, 31 citations in OpenAlex.
- Selinexor plus tislelizumab in patients with relapsed/refractory natural killer/T-cell lymphoma after failure of PD-1 blockade: the phase 1b TOUCH trial.The oncologist · 2026Article
- Lipin1-dependent transcriptional inactivation of SREBPs contributes to selinexor sensitivity in multiple myeloma.Acta pharmacologica Sinica · 2025Article
- Article
- KPT330 promotes the sensitivity of glioblastoma to olaparib by retaining SQSTM1 in the nucleus and disrupting lysosomal function.Autophagy · 2024Article
- p62 Is a Potential Biomarker for Risk of Malignant Transformation of Oral Potentially Malignant Disorders (OPMDs).Current issues in molecular biology · 2023Article
- CRM1 expression: association with high prognostic value in laryngeal cancer.Turkish journal of medical sciences · 2023Article
- Prediction of human protein interactome of dengue virus non-structural protein 5 (NS5) and its downstream immunological implications.3 Biotech · 2023Article
- Genome-Wide CRISPR-Cas9 Screen Identifies SMCHD1 as a Restriction Factor for Herpesviruses.mBio · 2023Article
- Druggable host gene dependencies in primary effusion lymphoma.Current opinion in virology · 2022Review
- Inhibition of XPO1 with KPT-330 induces autophagy-dependent apoptosis in gallbladder cancer by activating the p53/mTOR pathway.Journal of translational medicine · 2022Article
- Kaposi Sarcoma, a Trifecta of Pathogenic Mechanisms.Diagnostics (Basel, Switzerland) · 2022Review
- CRISPR/Cas9 application in cancer therapy: a pioneering genome editing tool.Cellular & molecular biology letters · 2022Review
- Article
- Kaposi's sarcoma-associated herpesvirus at 27.Tumour virus research · 2021Review
- Targeting the Kaposi's sarcoma-associated herpesvirus genome with the CRISPR-Cas9 platform in latently infected cells.Virology journal · 2021Article
- Targeting XPO1 enhances innate immune response and inhibits KSHV lytic replication during primary infection by nuclear stabilization of the p62 autophagy adaptor protein.Cell death & disease · 2021Article
- A Non-Coding RNA Network Involved in KSHV Tumorigenesis.Frontiers in oncology · 2021Article
- The Second-Generation XPO1 Inhibitor Eltanexor Inhibits Human Cytomegalovirus (HCMV) Replication and Promotes Type I Interferon Response.Frontiers in microbiology · 2021Article
- CSE1L, as a novel prognostic marker, promotes pancreatic cancer proliferation by regulating the AKT/mTOR signaling pathway.Journal of Cancer · 2021Article
- A CRISPR-Cas9 screen identifies mitochondrial translation as an essential process in latent KSHV infection of human endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
The abnormal proliferation of cancer cells is driven by deregulated oncogenes or tumor suppressors, among which the cancer-vulnerable genes are attractive therapeutic targets. Targeting mislocalization of oncogenes and tumor suppressors resulting from aberrant nuclear export is effective for inhibiting growth transformation of cancer cells. We performed a clustered regularly interspaced short palindromic repeat (CRISPR)-associated (Cas) screening in a unique model of matched primary and oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV)-transformed cells and identified genes that were growth promoting and growth suppressive for both types of cells, among which exportin XPO1 was demonstrated to be critical for the survival of transformed cells. Using XPO1 inhibitor KPT-8602 and by small interfering RNA (siRNA) knockdown, we confirmed the essential role of XPO1 in cell proliferation and growth transformation of KSHV-transformed cells and in cell lines of other cancers, including gastric cancer and liver cancer. XPO1 inhibition induced cell cycle arrest through p53 activation, but the mechanisms of p53 activation differed among the different types of cancer cells. p53 activation depended on the formation of promyelocytic leukemia (PML) nuclear bodies in gastric cancer and liver cancer cells. Mechanistically, XPO1 inhibition induced relocalization of autophagy adaptor protein p62 (SQSTM1), recruiting p53 for activation in PML nuclear bodies. Taken the data together, we have identified novel growth-promoting and growth-suppressive genes of primary and cancer cells and have demonstrated that XPO1 is a vulnerable target of cancer cells. XPO1 inhibition induces cell arrest through a novel PML- and p62-dependent mechanism of p53 activation in some types of cancer cells.
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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.