ArticleOncotarget2015
Simultaneous inhibition of deubiquitinating enzymes (DUBs) and autophagy synergistically kills breast cancer cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 52 citations in OpenAlex.
- Role of the USP family in autophagy regulation and cancer progression.Apoptosis : an international journal on programmed cell death · 2025Review
- Impairment of proteasome-associated deubiquitinating enzyme Uchl5/UBH-4 affects autophagy.Biology open · 2025Article
- Emerging potential of ubiquitin-specific proteases and ubiquitin-specific proteases inhibitors in breast cancer treatment.World journal of clinical cases · 2022Review
- The UCHL5 inhibitor b-AP15 overcomes cisplatin resistance via suppression of cancer stemness in urothelial carcinoma.Molecular therapy oncolytics · 2022Article
- Autophagy-related prognostic signature for survival prediction of triple negative breast cancer.PeerJ · 2022Article
- Comprehensive Target Screening and Cellular Profiling of the Cancer-Active Compound b-AP15 Indicate Abrogation of Protein Homeostasis and Organelle Dysfunction as the Primary Mechanism of Action.Frontiers in oncology · 2022Article
- Roles and Mechanisms of Deubiquitinases (DUBs) in Breast Cancer Progression and Targeted Drug Discovery.Life (Basel, Switzerland) · 2021Review
- Small Molecules Targeting Programmed Cell Death in Breast Cancer Cells.International journal of molecular sciences · 2021Review
- VLX1570 induces apoptosis through the generation of ROS and induction of ER stress on leukemia cell lines.Cancer science · 2021Article
- Dienone Compounds: Targets and Pharmacological Responses.Journal of medicinal chemistry · 2020Article
- Design, Synthesis, and Characterization of an Orally Active Dual-Specific ULK1/2 Autophagy Inhibitor that Synergizes with the PARP Inhibitor Olaparib for the Treatment of Triple-Negative Breast Cancer.Journal of medicinal chemistry · 2020Article
- Inhibition of 19S proteasome deubiquitinating activity in Schistosoma mansoni affects viability, oviposition, and structural changes.Parasitology research · 2020Article
- Drug Development Targeting the Ubiquitin-Proteasome System (UPS) for the Treatment of Human Cancers.Cancers · 2020Review
- Deubiquitinase Inhibitor b-AP15 Attenuated LPS-Induced Inflammation via Inhibiting ERK1/2, JNK, and NF-Kappa B.Frontiers in molecular biosciences · 2020Article
- The proteasome deubiquitinase inhibitor bAP15 downregulates TGF-β/Smad signaling and induces apoptosisOncotarget · 2019Article
- The Deubiquitinase Inhibitor b-AP15 and Its Effect on Phenotype and Function of Monocyte-Derived Dendritic Cells.Neoplasia (New York, N.Y.) · 2019Article
- Oxidative Stress Induced by the Deubiquitinase Inhibitor b-AP15 Is Associated with Mitochondrial Impairment.Oxidative medicine and cellular longevity · 2019Article
- Analysis of determinants for in vitro resistance to the small molecule deubiquitinase inhibitor b-AP15.PloS one · 2019Article
- Computational and biochemical studies of isothiocyanates as inhibitors of proteasomal cysteine deubiquitinases in human cancer cells.Journal of cellular biochemistry · 2018Article
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Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Breast cancer is one of the leading causes of cancer death among women in the United States. Patients expressing the estrogen and progesterone receptor (ER and PR) and human epidermal growth factor 2 (HER-2) tumor markers have favorable prognosis and efficacious therapeutic options. In contrast, tumors that are negative for these markers (triple-negative) have a disproportionate share of morbidity and mortality due to lack of a validated molecular target. Deubiquitinating enzymes (DUBs) are a critical component of ubiquitin-proteasome-system degradation and have been shown to be differentially expressed and activated in a number of cancers, including breast, with their aberrant activity linked to cancer prognosis and clinical outcome. We evaluated the effect of the DUB inhibitors b-AP15 and RA-9 alone and in combination with early- and late-stage lysosomal inhibitors on cell viability in a panel of triple negative breast cancer (TNBC) cell lines. Our results indicate small-molecule DUB inhibitors have a profound effect on TNBC viability and lead to activation of autophagy as a cellular mechanism to compensate for ubiquitin-proteasome-system stress. Treatment with sub-optimal doses of DUB and lysosome inhibitors synergistically kills TNBC cells. This supports the evaluation of DUB inhibition, in combination with lysosomal inhibition, as a therapeutic approach for the treatment of TNBC.
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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.