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Septin and Ras regulate cytokinetic abscission in detached cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Jilin Univ, Hosp 1, Changchun, Jilin, Peoples R China.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.ORCID iD: 0000-0003-2918-8142
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2019 (English)In: Cell Division, ISSN 1747-1028, E-ISSN 1747-1028, Vol. 14, no 1, article id 8Article in journal (Refereed) Published
Abstract [en]

Background Integrin-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. Results In 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. Conclusions Several 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.

Place, publisher, year, edition, pages
BMC , 2019. Vol. 14, no 1, article id 8
Keywords [en]
Cytokinesis, Bi-nucleation, Regression, Septin, Ras, Adhesion
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-398858DOI: 10.1186/s13008-019-0051-yISI: 000483550500002PubMedID: 31452675OAI: oai:DiVA.org:uu-398858DiVA, id: diva2:1377310
Funder
Swedish Cancer Society, CAN 2016/810Available from: 2019-12-11 Created: 2019-12-11 Last updated: 2019-12-11Bibliographically approved

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