ArticleCancer biology & therapy2015
USP9X inhibition promotes radiation-induced apoptosis in non-small cell lung cancer cells expressing mid-to-high MCL1.
Article in Cancer biology & therapy, 2015. 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, 33 citations in OpenAlex.
- Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options.Molecular cancer · 2024Review
- The Mechanism of Ubiquitination or Deubiquitination Modifications in Regulating Solid Tumor Radiosensitivity.Biomedicines · 2023Review
- Roles of USP9X in cellular functions and tumorigenesis (Review).Oncology letters · 2023Review
- Unlocking the potential of beta sitosterol: Augmenting the suppression of oral cancer cells through extrinsic and intrinsic signalling mechanisms.The Saudi dental journal · 2023Article
- Pro-apoptotic and anti-apoptotic regulation mediated by deubiquitinating enzymes.Cellular and molecular life sciences : CMLS · 2022Review
- Molecular mechanisms of the microRNA-132 during tumor progressions.Cancer cell international · 2021Review
- Stress Granules Involved in Formation, Progression and Metastasis of Cancer: A Scoping Review.Frontiers in cell and developmental biology · 2021Article
- USP9X Deubiquitylates DVL2 to Regulate WNT Pathway Specification.Cell reports · 2019Article
- SFI1 promotes centriole duplication by recruiting USP9X to stabilize the microcephaly protein STIL.The Journal of cell biology · 2019Article
- WP1130 Enhances TRAIL-Induced Apoptosis through USP9X-Dependent miR-708-Mediated Downregulation of c-FLIP.Cancers · 2019Article
- WP1130 reveals USP24 as a novel target in T-cell acute lymphoblastic leukemia.Cancer cell international · 2019Article
- Concurrent Inhibition of Pim and FLT3 Kinases Enhances Apoptosis of FLT3-ITD Acute Myeloid Leukemia Cells through Increased Mcl-1 Proteasomal Degradation.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- A novel USP9X substrate TTK contributes to tumorigenesis in non-small-cell lung cancer.Theranostics · 2018Article
- miR-132 suppresses the migration and invasion of lung cancer cells by blocking USP9X-induced epithelial-mesenchymal transition.American journal of translational research · 2018Article
- Loss of Usp9x disrupts cell adhesion, and components of the Wnt and Notch signaling pathways in neural progenitors.Scientific reports · 2017Article
- The importance of regulatory ubiquitination in cancer and metastasis.Cell cycle (Georgetown, Tex.) · 2017Review
- The Emerging Role of Non-traditional Ubiquitination in Oncogenic Pathways.The Journal of biological chemistry · 2017Review
- USP9X, a Putative Tumor Suppressor Gene, Exhibits Frameshift Mutations in Colorectal Cancers.Pathology oncology research : POR · 2017Article
- Clinical outcomes of EGFR-TKI treatment and genetic heterogeneity in lung adenocarcinoma patients with EGFR mutations on exons 19 and 21.Chinese journal of cancer · 2016Article
- Inhibition of deubiquitinases primes glioblastoma cells to apoptosis in vitro and in vivo.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
background and purposeRadiotherapy (RT) is vital for the treatment of locally advanced non-small cell lung cancer (NSCLC), yet its delivery is limited by tolerances of adjacent organs. We sought therefore to identify and characterize gene targets whose inhibition may improve RT. MATERIALS AND
methodsWhole genome pooled shRNA cytotoxicity screens were performed in A549 and NCI-H460 using a retroviral library of 74,705 sequences. Cells were propagated with or without daily radiation Monday-Friday. Radiosensitization by top differential dropout hits was assessed by clonogenic assays. Apoptosis was assessed using a caspase 3/7 cell-based activity assay and by annexin V-FITC and PI staining. MCL1 expression was assessed by qPCR and Western blotting.
resultsUSP9X, a deubiquitinase, was a top hit among druggable gene products. WP1130, a small molecule USP9X inhibitor, showed synergistic cytotoxicity with IR. MCL1, an anti-apoptotic protein deubiquitinated by USP9X, decreased with USP9X inhibition and IR. This was accompanied by increases in caspase 3/7 activity and apoptosis. In a panel of NSCLC lines, MCL1 and USP9X protein and gene expression levels were highly correlated. Lines showing high levels of MCL1 expression were the most sensitive to USP9X inhibition.
conclusionsThese data support the use of MCL1 expression as a predictive biomarker for USP9X inhibitors in NSCLC therapy.
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