{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gupta DK"],"funding":["Swedish Cancer Foundation"],"pagination":["8"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6702736"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14"],"pubmed_abstract":["<h4>Background</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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."],"journal":["Cell division"],"pubmed_title":["Septin and Ras regulate cytokinetic abscission in detached cells."],"pmcid":["PMC6702736"],"funding_grant_id":["CAN 2016/810"],"pubmed_authors":["Gupta DK","Liu L","Johansson S","Kamranvar SA","Du J"],"additional_accession":[]},"is_claimable":false,"name":"Septin and Ras regulate cytokinetic abscission in detached cells.","description":"<h4>Background</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019","modification":"2024-11-11T21:41:27.716Z","creation":"2019-08-31T07:06:47Z"},"accession":"S-EPMC6702736","cross_references":{"pubmed":["31452675"],"doi":["10.1186/s13008-019-0051-y"]}}