Centrosome reduction in newly-generated tetraploid cancer cells obtained by separase depletion
Galofré, Claudia (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Asensio, Elena (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Ubach, Maria (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Torres, Irianna M. (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Quintanilla, Isabel (National Institutes of Health. National Cancer Institute)
Castells, Antoni (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Camps, Jordi (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Data:	2020
Resum:	Tetraploidy, a common feature in cancer, results in the presence of extra centrosomes, which has been associated with chromosome instability (CIN) and aneuploidy. Deregulation in the number of centrosomes triggers tumorigenesis. However, how supernumerary centrosomes evolve during the emergence of tetraploid cells remains yet to be elucidated. Here, generating tetraploid isogenic clones in colorectal cancer and in non-transformed cells, we show that near-tetraploid clones exhibit a significant increase in the number of centrosomes. Moreover, we find that centrosome area in near-tetraploids is twice as large as in near-diploids. To evaluate whether centrosome clustering was occurring, we next analysed the number of centrioles revealing centriole amplification. Notwithstanding, more than half of the near-tetraploids maintained in culture do not present centrosome aberrations. To test whether cells progressively lost centrioles after becoming near-tetraploid, we transiently transfected diploid cells with siRNA against ESPL1 /Separase, a protease responsible for triggering anaphase, to generate newly near-tetraploid cells. Finally, using this model, we assessed the number of centrioles at different time-points after tetraploidization finding that near-tetraploids rapidly lose centrosomes over time. Taken together, these data demonstrate that although most cells reduce supernumerary centrosomes after tetraploidization, a small fraction retains extra centrioles, potentially resulting in CIN.
Ajuts:	Instituto de Salud Carlos III CPII18/00026 Instituto de Salud Carlos III PI14/00783 Instituto de Salud Carlos III PI17/01304 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1035
Nota:	Altres ajuts: Fundación Científica de la Asociación Española Contra el Cáncer (GCB13131592CAST)
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Chromosome segregation ; Mitosis ; Centrosome ; Cancer genetics
Publicat a:	Scientific reports, Vol. 10 (June 2020) , art. 9152, ISSN 2045-2322

DOI: 10.1038/s41598-020-65975-1
PMID: 32499568

12 p, 4.2 MB

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