Tetraploidy as a metastable state towards malignant cell transformation within a systemic approach of cancer development.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101632149 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3592 (Electronic) Linking ISSN: 13835718 NLM ISO Abbreviation: Mutat Res Genet Toxicol Environ Mutagen Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam : Elsevier, 1997-
    • Subject Terms:
      Tetraploidy* ; Cell Transformation, Neoplastic*/genetics ; Neoplasms*/genetics ; Neoplasms*/pathology; Humans ; Animals ; Epigenesis, Genetic ; Aneuploidy ; Cellular Senescence/genetics
    • Abstract:
      Tetraploidy, a condition in which a cell has four homologous sets of chromosomes, may be a natural physiological condition or pathophysiological such as in cancer cells or stress induced tetraploidisation. Its contribution to cancer development is well known. However, among the many models proposed to explain the causes, mechanisms and steps of malignant cell transformation, only few integrate tetraploidization into a systemic multistep approach of carcinogenesis. Therefore, we will i) describe the molecular and cellular characteristics of tetraploidy; ii) assess the contribution of stress-induced tetraploidy in cancer development; iii) situate tetraploidy as a metastable state leading to cancer development in a systemic cell-centered approach; iiii) consider knowledge gaps and future perspectives. The available data shows that stress-induced tetraploidisation/polyploidisation leads to p53 stabilisation, cell cycle arrest, followed by cellular senescence or apoptosis, suppressing the proliferation of tetraploid cells. However, if tetraploid cells escape the G1-tetraploidy checkpoint, it may lead to uncontrolled proliferation of tetraploid cells, micronuclei induction, aneuploidy and deploidisation. In addition, tetraploidization favors 3D-chromatin changes and epigenetic effects. The combined effects of genetic and epigenetic changes allow the expression of oncogenic gene expression and cancer progression. Moreover, since micronuclei are inducing inflammation, which in turn may induce additional tetraploidization, tetraploidy-derived genetic instability leads to a carcinogenic vicious cycle. The concept that polyploid cells are metastable intermediates between diploidy and aneuploidy is not new. Metastability denotes an intermediate energetic state within a dynamic system other than the system's state at least energy. Considering in parallel the genetic/epigenetic changes and the probable entropy levels induced by stress-induced tetraploidisation provides a new systemic approach to describe cancer development.
      Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Aneuploidy; Cancer; Entropy; Micronuclei; Systemic; Tetraploidy
    • Publication Date:
      Date Created: 20240531 Date Completed: 20240531 Latest Revision: 20240604
    • Publication Date:
      20240604
    • Accession Number:
      10.1016/j.mrgentox.2024.503764
    • Accession Number:
      38821671