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CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies

Cell division cycle 20 homologue (CDC20) is a well-known regulator of cell cycle, as it controls the correct segregation of chromosomes during mitosis. Many studies have focused on the biological role of CDC20 in cancer development, as alterations of its functionality have been linked to genomic ins...

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Autores principales: Bruno, Samantha, Ghelli Luserna di Rorà, Andrea, Napolitano, Roberta, Soverini, Simona, Martinelli, Giovanni, Simonetti, Giorgia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9055704/
https://www.ncbi.nlm.nih.gov/pubmed/35490245
http://dx.doi.org/10.1186/s13046-022-02363-9
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author Bruno, Samantha
Ghelli Luserna di Rorà, Andrea
Napolitano, Roberta
Soverini, Simona
Martinelli, Giovanni
Simonetti, Giorgia
author_facet Bruno, Samantha
Ghelli Luserna di Rorà, Andrea
Napolitano, Roberta
Soverini, Simona
Martinelli, Giovanni
Simonetti, Giorgia
author_sort Bruno, Samantha
collection PubMed
description Cell division cycle 20 homologue (CDC20) is a well-known regulator of cell cycle, as it controls the correct segregation of chromosomes during mitosis. Many studies have focused on the biological role of CDC20 in cancer development, as alterations of its functionality have been linked to genomic instability and evidence demonstrated that high CDC20 expression levels are associated with poor overall survival in solid cancers. More recently, novel CDC20 functions have been demonstrated or suggested, including the regulation of apoptosis and stemness properties and a correlation with immune cell infiltration. Here, we here summarize and discuss the role of CDC20 inside and outside mitosis, starting from its network of interacting proteins. In the last years, CDC20 has also attracted more interest in the blood cancer field, being overexpressed and showing an association with prognosis both in myeloid and lymphoid malignancies. Preclinical findings showed that selective CDC20 and APC/C(CDC20)/APC/C(CDH1) inhibitors, namely Apcin and proTAME, are effective against lymphoma and multiple myeloma cells, resulting in mitotic arrest and apoptosis and synergizing with clinically-relevant drugs. The evidence and hypothesis presented in this review provide the input for further biological and chemical studies aiming to dissect novel potential CDC20 roles and targeting strategies in hematological malignancies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-022-02363-9.
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spelling pubmed-90557042022-05-01 CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies Bruno, Samantha Ghelli Luserna di Rorà, Andrea Napolitano, Roberta Soverini, Simona Martinelli, Giovanni Simonetti, Giorgia J Exp Clin Cancer Res Review Cell division cycle 20 homologue (CDC20) is a well-known regulator of cell cycle, as it controls the correct segregation of chromosomes during mitosis. Many studies have focused on the biological role of CDC20 in cancer development, as alterations of its functionality have been linked to genomic instability and evidence demonstrated that high CDC20 expression levels are associated with poor overall survival in solid cancers. More recently, novel CDC20 functions have been demonstrated or suggested, including the regulation of apoptosis and stemness properties and a correlation with immune cell infiltration. Here, we here summarize and discuss the role of CDC20 inside and outside mitosis, starting from its network of interacting proteins. In the last years, CDC20 has also attracted more interest in the blood cancer field, being overexpressed and showing an association with prognosis both in myeloid and lymphoid malignancies. Preclinical findings showed that selective CDC20 and APC/C(CDC20)/APC/C(CDH1) inhibitors, namely Apcin and proTAME, are effective against lymphoma and multiple myeloma cells, resulting in mitotic arrest and apoptosis and synergizing with clinically-relevant drugs. The evidence and hypothesis presented in this review provide the input for further biological and chemical studies aiming to dissect novel potential CDC20 roles and targeting strategies in hematological malignancies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-022-02363-9. BioMed Central 2022-04-30 /pmc/articles/PMC9055704/ /pubmed/35490245 http://dx.doi.org/10.1186/s13046-022-02363-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Bruno, Samantha
Ghelli Luserna di Rorà, Andrea
Napolitano, Roberta
Soverini, Simona
Martinelli, Giovanni
Simonetti, Giorgia
CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies
title CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies
title_full CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies
title_fullStr CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies
title_full_unstemmed CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies
title_short CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies
title_sort cdc20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9055704/
https://www.ncbi.nlm.nih.gov/pubmed/35490245
http://dx.doi.org/10.1186/s13046-022-02363-9
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