Over-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregation

Gaëlle Marteil (), Adan Guerrero, André F. Vieira, Bernardo P. de Almeida, Pedro Machado, Susana Mendonça, Marta Mesquita, Beth Villarreal, Irina Fonseca, Maria E. Francia, Katharina Dores, Nuno P. Martins, Swadhin C. Jana, Erin M. Tranfield, Nuno L. Barbosa-Morais, Joana Paredes, David Pellman, Susana A. Godinho and Mónica Bettencourt-Dias ()
Additional contact information
Gaëlle Marteil: Instituto Gulbenkian de Ciência
Adan Guerrero: Instituto Gulbenkian de Ciência
André F. Vieira: Universidade do Porto
Bernardo P. de Almeida: Universidade de Lisboa
Pedro Machado: Instituto Gulbenkian de Ciência
Susana Mendonça: Instituto Gulbenkian de Ciência
Marta Mesquita: Instituto Português de Oncologia de Lisboa
Beth Villarreal: Novartis Institutes for BioMedical Research
Irina Fonseca: Instituto Gulbenkian de Ciência
Maria E. Francia: Instituto Gulbenkian de Ciência
Katharina Dores: Instituto Gulbenkian de Ciência
Nuno P. Martins: Instituto Gulbenkian de Ciência
Swadhin C. Jana: Instituto Gulbenkian de Ciência
Erin M. Tranfield: Instituto Gulbenkian de Ciência
Nuno L. Barbosa-Morais: Universidade de Lisboa
Joana Paredes: Universidade do Porto
David Pellman: Dana-Faber Cancer Institute
Susana A. Godinho: Dana-Faber Cancer Institute
Mónica Bettencourt-Dias: Instituto Gulbenkian de Ciência

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: Abstract Centrosomes are the major microtubule organising centres of animal cells. Deregulation in their number occurs in cancer and was shown to trigger tumorigenesis in mice. However, the incidence, consequence and origins of this abnormality are poorly understood. Here, we screened the NCI-60 panel of human cancer cell lines to systematically analyse centriole number and structure. Our screen shows that centriole amplification is widespread in cancer cell lines and highly prevalent in aggressive breast carcinomas. Moreover, we identify another recurrent feature of cancer cells: centriole size deregulation. Further experiments demonstrate that severe centriole over-elongation can promote amplification through both centriole fragmentation and ectopic procentriole formation. Furthermore, we show that overly long centrioles form over-active centrosomes that nucleate more microtubules, a known cause of invasiveness, and perturb chromosome segregation. Our screen establishes centriole amplification and size deregulation as recurrent features of cancer cells and identifies novel causes and consequences of those abnormalities.

Date: 2018
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DOI: 10.1038/s41467-018-03641-x

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