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Tetraploid Cells in Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 7328

Special Issue Editor

1. Department of Laboratory Medicine, Translational Cancer Research, Lund University, Medicon Village, 223 81 Lund, Sweden
2. Laboratory of Molecular Biotechnology of Eukaryotes, Sfax Biotechnology Centre, Sfax University, Sfax, Tunisia
Interests: cell death; mitotic catastrophe; genomic instability; metastasis; migration; cancer

Special Issue Information

Dear Colleagues, 

Tetraploidization is the condition of having twice as many chromosomes as their normal, diploid counterparts. With the exception of some physiological statuses, cells do not tolerate the tetraploidy and activate programmed death pathways or elicit immune responses resulting in their elimination. However, tetraploidy can constitute a metastable intermediate between healthy diploidy and neoplastic aneuploidy. Indeed, tetraploid cells are detected in many cancers and are associated with cancer progression and aggressiveness, as well as therapeutic resistance and poor prognosis. 

This Special Issue aims at presenting current status, recent developments, and future directions of research on tetraploid genomic status with emphasis on the following topics, but not only: 

  • Cancer research;
  • Treatment therapy failure;
  • Tetraploid stem cells;
  • Animal models to study the disease mechanism of tetraploidization;
  • Illicit survival of tetraploid cancer cells;
  • Cancer metastasis provoked by tetraploidization. 

Dr. Mohamed Jemaà
Guest Editor

Manuscript Submission Information

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Keywords

  • polyploidy
  • tetraploidy
  • metastasis
  • cancer
  • polyploidazation
  • therapy
  • stem cells
  • radiotherapy
  • microtubules
  • centrosomes
  • mitotic chekpoints

Published Papers (3 papers)

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Research

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13 pages, 4287 KiB  
Article
Tetraploidization Increases the Motility and Invasiveness of Cancer Cells
by Mohamed Jemaà, Renee Daams, Slim Charfi, Fredrik Mertens, Stephan M. Huber and Ramin Massoumi
Int. J. Mol. Sci. 2023, 24(18), 13926; https://doi.org/10.3390/ijms241813926 - 10 Sep 2023
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Abstract
Polyploidy and metastasis are associated with a low probability of disease-free survival in cancer patients. Polyploid cells are known to facilitate tumorigenesis. However, few data associate polyploidization with metastasis. Here, by generating and using diploid (2n) and tetraploid (4n) clones from malignant fibrous [...] Read more.
Polyploidy and metastasis are associated with a low probability of disease-free survival in cancer patients. Polyploid cells are known to facilitate tumorigenesis. However, few data associate polyploidization with metastasis. Here, by generating and using diploid (2n) and tetraploid (4n) clones from malignant fibrous histiocytoma (MFH) and colon carcinoma (RKO), we demonstrate the migration and invasion advantage of tetraploid cells in vitro using several assays, including the wound healing, the OrisTM two-dimensional cell migration, single-cell migration tracking by video microscopy, the Boyden chamber, and the xCELLigence RTCA real-time cell migration. Motility advantage was observed despite tetraploid cell proliferation weakness. We could also demonstrate preferential metastatic potential in vivo for the tetraploid clone using the tail vein injection in mice and tracking metastatic tumors in the lung. Using the Mitelman Database of Chromosome Aberrations in Cancer, we found an accumulation of polyploid karyotypes in metastatic tumors compared to primary ones. This work reveals the clinical relevance of the polyploid subpopulation and the strategic need to highlight polyploidy in preclinical studies as a therapeutic target for metastasis. Full article
(This article belongs to the Special Issue Tetraploid Cells in Health and Disease)
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Review

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20 pages, 1855 KiB  
Review
Involvement of Bcl-2 Family Proteins in Tetraploidization-Related Senescence
by Daniel Barriuso, Lucia Alvarez-Frutos, Lucia Gonzalez-Gutierrez, Omar Motiño, Guido Kroemer, Roberto Palacios-Ramirez and Laura Senovilla
Int. J. Mol. Sci. 2023, 24(7), 6374; https://doi.org/10.3390/ijms24076374 - 28 Mar 2023
Cited by 1 | Viewed by 2537
Abstract
The B-cell lymphoma 2 (Bcl-2) family of proteins is the main regulator of apoptosis. However, multiple emerging evidence has revealed that Bcl-2 family proteins are also involved in cellular senescence. On the one hand, the different expression of these proteins determines the entry [...] Read more.
The B-cell lymphoma 2 (Bcl-2) family of proteins is the main regulator of apoptosis. However, multiple emerging evidence has revealed that Bcl-2 family proteins are also involved in cellular senescence. On the one hand, the different expression of these proteins determines the entry into senescence. On the other hand, entry into senescence modulates the expression of these proteins, generally conferring resistance to apoptosis. With some exceptions, senescent cells are characterized by the upregulation of antiapoptotic proteins and downregulation of proapoptotic proteins. Under physiological conditions, freshly formed tetraploid cells die by apoptosis due to the tetraploidy checkpoint. However, suppression of Bcl-2 associated x protein (Bax), as well as overexpression of Bcl-2, favors the appearance and survival of tetraploid cells. Furthermore, it is noteworthy that our laboratory has shown that the joint absence of Bax and Bcl-2 antagonist/killer (Bak) favors the entry into senescence of tetraploid cells. Certain microtubule inhibitory chemotherapies, such as taxanes and vinca alkaloids, induce the generation of tetraploid cells. Moreover, the combined use of inhibitors of antiapoptotic proteins of the Bcl-2 family with microtubule inhibitors increases their efficacy. In this review, we aim to shed light on the involvement of the Bcl-2 family of proteins in the senescence program activated after tetraploidization and the possibility of using this knowledge to create a new therapeutic strategy targeting cancer cells. Full article
(This article belongs to the Special Issue Tetraploid Cells in Health and Disease)
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16 pages, 662 KiB  
Review
Whole-Genome Duplication and Genome Instability in Cancer Cells: Double the Trouble
by Tsz Yin Lau and Randy Y.C. Poon
Int. J. Mol. Sci. 2023, 24(4), 3733; https://doi.org/10.3390/ijms24043733 - 13 Feb 2023
Cited by 1 | Viewed by 2994
Abstract
Whole-genome duplication (WGD) is one of the most common genomic abnormalities in cancers. WGD can provide a source of redundant genes to buffer the deleterious effect of somatic alterations and facilitate clonal evolution in cancer cells. The extra DNA and centrosome burden after [...] Read more.
Whole-genome duplication (WGD) is one of the most common genomic abnormalities in cancers. WGD can provide a source of redundant genes to buffer the deleterious effect of somatic alterations and facilitate clonal evolution in cancer cells. The extra DNA and centrosome burden after WGD is associated with an elevation of genome instability. Causes of genome instability are multifaceted and occur throughout the cell cycle. Among these are DNA damage caused by the abortive mitosis that initially triggers tetraploidization, replication stress and DNA damage associated with an enlarged genome, and chromosomal instability during the subsequent mitosis in the presence of extra centrosomes and altered spindle morphology. Here, we chronicle the events after WGD, from tetraploidization instigated by abortive mitosis including mitotic slippage and cytokinesis failure to the replication of the tetraploid genome, and finally, to the mitosis in the presence of supernumerary centrosomes. A recurring theme is the ability of some cancer cells to overcome the obstacles in place for preventing WGD. The underlying mechanisms range from the attenuation of the p53-dependent G1 checkpoint to enabling pseudobipolar spindle formation via the clustering of supernumerary centrosomes. These survival tactics and the resulting genome instability confer a subset of polyploid cancer cells proliferative advantage over their diploid counterparts and the development of therapeutic resistance. Full article
(This article belongs to the Special Issue Tetraploid Cells in Health and Disease)
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