Acute degradation of nucleolin reveals its novel functions in cell cycle progression and cell division in triple negative breast cancer
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Le résumé fourni par la source
INTRODUCTION: Nucleoli are large nuclear sub-compartments where vital processes, such as ribosome assembly, take place. Most nucleolar proteins are essential; thus, their abrogation cannot be achieved through conventional approaches. This technical obstacle has limited our understanding of the biological functions of nucleolar proteins in cell homeostasis and cancer pathogenesis. METHODS: We applied the Auxin Inducible Degron (AID) proteolytic system, paired with CRISPR/Cas9 knock-in gene-editing, to obtain an unprecedented characterization of the biological activities of Nucleolin (NCL), one of the most abundant nucleolar proteins, in Triple Negative Breast Cancer (TNBC) cells. Then, we combined live-cell imaging, RNA-sequencing, and quantitative proteomics, to characterize the impact of NCL acute abrogation on the behavior of TNBC cells. Finally, we used in silico analyses to validate NCL molecular role in TNBC patients. RESULTS: Acute abrogation of endogenous NCL impacted both the transcriptome and the proteome of TNBC cells, particularly affecting critical players involved in ribosome biogenesis and in cell cycle progression. Unexpectedly, NCL depletion limited cancer cell ability to effectively complete cytokinesis, ultimately leading to the accumulation of bi-nucleated cells. In silico analyses confirmed that the levels of regulators of cell cycle progression and chromosome segregation correlated with NCL abundance in TNBC patients. Finally, NCL degradation enhanced the activity of pharmaceutical inhibitors of cellular mitosis, such as the Anaphase Promoting Complex inhibitor APCin. CONCLUSIONS: Our findings indicate a novel role for NCL in supporting the completion of the cell division in TNBC models, and that its abrogation could enhance the therapeutic activity of mitotic-progression inhibitors.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Acute degradation of nucleolin reveals its novel functions in cell cycle progression and cell division in triple negative breast cancer
- Date Crossref
- 14/07/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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The Ohio State University Wexner Medical Center and Developmental Biology Graduate Program pays non établi dans la noticeÉtablissement de santé
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The Ohio State University Pelotonia Institute for Immuno-Oncology pays non établi dans la noticeUniversité ou école supérieure
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Tufts University pays non établi dans la noticeUniversité ou école supérieure
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Institute for Biomedical Research and Innovation pays non établi dans la noticeStructure de recherche
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Tulane University Current address: Department of Ecology and Evolutionary Biology pays non établi dans la noticeUniversité ou école supérieure
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The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute pays non établi dans la noticeÉtablissement de santé
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National Cancer Institute pays non établi dans la noticeOrganisme public
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Department of Health and Human Services pays non établi dans la noticeOrganisme public
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Oregon Health & Science University pays non établi dans la noticeUniversité ou école supérieure
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College of Medicine Department of Cancer Biology and Genetics pays non établi dans la noticeUniversité ou école supérieure
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Oncology Unit pays non établi dans la noticeInstitution
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Graduate School of Biomedical Sciences pays non établi dans la noticeUniversité ou école supérieure
and Developmental Biology Graduate Program — The Ohio State University Wexner Medical Center, Pelotonia Institute for Immuno-Oncology — The Ohio State University et Tufts University, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.