ArticleProceedings of the National Academy of Sciences of the United States of America2011
A cyclin-D1 interaction with BAX underlies its oncogenic role and potential as a therapeutic target in mantle cell lymphoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 56 citations in OpenAlex.
- Low-Dose Ionizing Radiation and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Review of Recent Evidence and Future Research Directions Toward the Elucidation of a Metabolic, Immunologic, and Signaling Cascade.International journal of molecular sciences · 2026Review
- Exploring the role of cyclin D1 in the pathogenesis of multiple myeloma beyond cell cycle regulation.Molecular oncology · 2025Article
- Combination venetoclax and selinexor effective in relapsed refractory multiple myeloma with translocation t(11;14).NPJ precision oncology · 2022Article
- BH3 Mimetics in Hematologic Malignancies.International journal of molecular sciences · 2021Review
- Targeting BCL-2 in B-cell malignancies and overcoming therapeutic resistance.Cell death & disease · 2020Review
- Molecular Pathogenesis of Mantle Cell Lymphoma.Hematology/oncology clinics of North America · 2020Review
- Iron chelation and 2-oxoglutarate-dependent dioxygenase inhibition suppress mantle cell lymphoma's cyclin D1.Journal of cellular and molecular medicine · 2019Article
- Proapoptotic protein BIM as a novel prognostic marker in mantle cell lymphoma.Human pathology · 2019Article
- Dynamic molecular monitoring reveals that SWI-SNF mutations mediate resistance to ibrutinib plus venetoclax in mantle cell lymphoma.Nature medicine · 2019Article
- Targeting the anion exchanger 2 with specific peptides as a new therapeutic approach in B lymphoid neoplasms.Haematologica · 2018Article
- Lipid nanoparticle siRNA cocktails for the treatment of mantle cell lymphoma.Bioengineering & translational medicine · 2018Article
- Role of SOX11 and Genetic Events Cooperating with Cyclin D1 in Mantle Cell Lymphoma.Current oncology reports · 2017Review
- Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies.Nature communications · 2017Article
- Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics.Nature communications · 2016Article
- Non-canonical functions of cell cycle cyclins and cyclin-dependent kinases.Nature reviews. Molecular cell biology · 2016Review
- Article
- Cyclin D1 sensitizes myeloma cells to endoplasmic reticulum stress-mediated apoptosis by activating the unfolded protein response pathway.BMC cancer · 2015Article
- S-palmitoylation represents a novel mechanism regulating the mitochondrial targeting of BAX and initiation of apoptosis.Cell death & disease · 2014Article
- Article
- Lineage-specific function of Engrailed-2 in the progression of chronic myelogenous leukemia to T-cell blast crisis.Cell cycle (Georgetown, Tex.) · 2014Article
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Authors and funding
18 authors at 9 institutions in 3 countries.
Funding
Abstract
The chromosomal translocation t(11;14)(q13;q32) leading to cyclin-D1 overexpression plays an essential role in the development of mantle cell lymphoma (MCL), an aggressive tumor that remains incurable with current treatment strategies. Cyclin-D1 has been postulated as an effective therapeutic target, but the evaluation of this target has been hampered by our incomplete understanding of its oncogenic functions and by the lack of valid MCL murine models. To address these issues, we generated a cyclin-D1-driven mouse model in which cyclin-D1 expression can be regulated externally. These mice developed cyclin-D1-expressing lymphomas capable of recapitulating features of human MCL. We found that cyclin-D1 inactivation was not sufficient to induce lymphoma regression in vivo; however, using a combination of in vitro and in vivo assays, we identified a novel prosurvival cyclin-D1 function in MCL cells. Specifically, we found that cyclin-D1, besides increasing cell proliferation through deregulation of the cell cycle at the G(1)-S transition, sequestrates the proapoptotic protein BAX in the cytoplasm, thereby favoring BCL2's antiapoptotic function. Accordingly, cyclin-D1 inhibition sensitized the lymphoma cells to apoptosis through BAX release. Thus, genetic or pharmacologic targeting of cyclin-D1 combined with a proapoptotic BH3 mimetic synergistically killed the cyclin-D1-expressing murine lymphomas, human MCL cell lines, and primary lymphoma cells. Our study identifies a role of cyclin-D1 in deregulating apoptosis in MCL cells, and highlights the potential benefit of simultaneously targeting cyclin-D1 and survival pathways in patients with MCL. This effective combination therapy also might be exploited in other cyclin-D1-expressing tumors.
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