ArticleOncotarget2016
Identification of the APC/C co-factor FZR1 as a novel therapeutic target for multiple myeloma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- A novel ubiquitination-based molecular signature predicts prognosis in diffuse large B-cell lymphoma.Annals of hematology · 2025Article
- USP5 motivates immunosuppressive microenvironment in multiple myeloma by activating STAT2-PFKFB4-mediated glycolysis.Cancer immunology, immunotherapy : CII · 2025Article
- Targeting the anaphase-promoting complex/cyclosome (APC/C) enhanced antiproliferative and apoptotic response in bladder cancer.Saudi journal of biological sciences · 2023Article
- 5-methylcytosine RNA methyltransferases and their potential roles in cancer.Journal of translational medicine · 2022Review
- CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies.Journal of experimental & clinical cancer research : CR · 2022Review
- The chemotherapeutic CX-5461 primarily targets TOP2B and exhibits selective activity in high-risk neuroblastoma.Nature communications · 2021Article
- RNA methyltransferase NSUN2 promotes growth of hepatocellular carcinoma cells by regulating fizzy-related-1 in vitro and in vivo.The Kaohsiung journal of medical sciences · 2021Article
- A Novel Signature of CCNF-Associated E3 Ligases Collaborate and Counter Each Other in Breast Cancer.Cancers · 2021Article
- Identification of Susceptible Genes for Chronic Obstructive Pulmonary Disease with Lung Adenocarcinoma by Weighted Gene Co-Expression Network Analysis.OncoTargets and therapy · 2021Article
- APC/C ubiquitin ligase: Functions and mechanisms in tumorigenesis.Seminars in cancer biology · 2020Review
- The E3 ligase HUWE1 inhibition as a therapeutic strategy to target MYC in multiple myeloma.Oncogene · 2020Article
- The Identification of Potential Therapeutic Targets for Cutaneous Squamous Cell Carcinoma.The Journal of investigative dermatology · 2020Article
- Paradoxical mitotic exit induced by a small molecule inhibitor of APC/CNature chemical biology · 2020Article
- The anaphase-promoting complex/cyclosome: a new promising target in diffuse large B-cell lymphoma and mantle cell lymphoma.British journal of cancer · 2019Article
- TRAF6 Silencing Attenuates Multiple Myeloma Cell Adhesion to Bone Marrow Stromal Cells.International journal of molecular sciences · 2019Article
- The Air Sac Primordium ofInternational journal of molecular sciences · 2018Review
- Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple Myeloma (MM) is a haematological neoplasm characterised by the clonal proliferation of malignant plasma cells in the bone marrow. The success of proteasome inhibitors in the treatment of MM has highlighted the importance of the ubiquitin proteasome system (UPS) in the pathogenesis of this disease. In this study, we analysed gene expression of UPS components to identify novel therapeutic targets within this pathway in MM. Here we demonstrate how this approach identified previously validated and novel therapeutic targets. In addition we show that FZR1 (Fzr), a cofactor of the multi-subunit E3 ligase complex anaphase-promoting complex/cyclosome (APC/C), represents a novel therapeutic target in myeloma. The APC/C associates independently with two cofactors, Fzr and Cdc20, to control cell cycle progression. We found high levels of FZR1 in MM primary cells and cell lines and demonstrate that expression is further increased on adhesion to bone marrow stromal cells (BMSCs). Specific knockdown of either FZR1 or CDC20 reduced viability and induced growth arrest of MM cell lines, and resulted in accumulation of APC/CFzr substrate Topoisomerase IIα (TOPIIα) or APC/CCdc20 substrate Cyclin B. Similar effects were observed following treatment with proTAME, an inhibitor of both APC/CFzr and APC/CCdc20. Combinations of proTAME with topoisomerase inhibitors, etoposide and doxorubicin, significantly increased cell death in MM cell lines and primary cells, particularly if TOPIIα levels were first increased through pre-treatment with proTAME. Similarly, combinations of proTAME with the microtubule inhibitor vincristine resulted in enhanced cell death. This study demonstrates the potential of targeting the APC/C and its cofactors as a therapeutic approach in MM.
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