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Septin and Ras regulate cytokinetic abscission in detached cells

Authors
  • Gupta, Deepesh Kumar1
  • Kamranvar, Siamak A.1
  • Du, Jian1, 2
  • Liu, Liangwen1
  • Johansson, Staffan1
  • 1 Uppsala University, Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala, 751 23, Sweden , Uppsala (Sweden)
  • 2 First Hospital of Jilin University, Changchun, Jilin, China , Changchun (China)
Type
Published Article
Journal
Cell Division
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Aug 21, 2019
Volume
14
Issue
1
Identifiers
DOI: 10.1186/s13008-019-0051-y
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundIntegrin-mediated adhesion is normally required for cytokinetic abscission, and failure in the process can generate potentially oncogenic tetraploid cells. Here, detachment-induced formation of oncogenic tetraploid cells was analyzed in non-transformed human BJ fibroblasts and BJ expressing SV40LT (BJ-LT) ± overactive HRas.ResultsIn contrast to BJ and BJ-LT cells, non-adherent BJ-LT-Ras cells recruited ALIX and CHMP4B to the midbody and divided. In detached BJ and BJ-LT cells regression of the cytokinetic furrow was suppressed by intercellular bridge-associated septin; after re-adhesion these cells divided by cytofission, however, some cells became bi-nucleated because of septin reorganization and furrow regression. Adherent bi-nucleated BJ cells became senescent in G1 with p21 accumulation in the nucleus, apparently due to p53 activation since adherent bi-nucleated BJ-LT cells passed through next cell cycle and divided into mono-nucleated tetraploids; the two centrosomes present in bi-nucleated BJ cells fused after furrow regression, pointing to the PIDDosome pathway as a possible mechanism for the p53 activation.ConclusionsSeveral mechanisms prevent detached normal cells from generating tumor-causing tetraploid cells unless they have a suppressed p53 response by viruses, mutation or inflammation. Importantly, activating Ras mutations promote colony growth of detached transformed cells by inducing anchorage-independent cytokinetic abscission in single cells.

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