Journal Article

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

de Almeida, Bernardo P., Pellman, David, Francia, Maria E., Marteil, Gaëlle, Barbosa-Morais, Nuno L., Vieira, André F., Machado, Pedro, Godinho, Susana A., Tranfield, Erin M., Dores, Katharina, Mendonça, Susana, Villarreal, Beth, Martins, Nuno P., Jana, Swadhin C., Bettencourt-Dias, Mónica, Mesquita, Marta, Guerrero, Adan, Paredes, Joana, Fonseca, Irina

2018

Overview

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. Cancer cells are characterised by abnormalities in the number of centrosomes and this phenotype is linked with tumorigenesis. Here the authors report centriole length deregulation in a subset of cancer cell lines and suggest a link with subsequent alterations in centriole numbers and chromosomal instability.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/51 / 14 / 14/1 / 14/28 / 14/63 / 631/67 / 631/80/128/1965 / 82/80 / Abnormalities / Amplification / Automation / Biotechnology / Breast cancer / Breast carcinoma / Breast Neoplasms - metabolism / Cancer / Cell Cycle - physiology / Cell Cycle Proteins - metabolism / Cell Line, Tumor / Centrioles / Centrioles - metabolism / Centrosome - metabolism / Centrosomes / Chromosomes - ultrastructure / Deregulation / Elongation / Humanities and Social Sciences / Humans / Invasiveness / Life Sciences / Microscopy, Electron, Transmission / Microtubule-Associated Proteins - metabolism / Microtubules / Microtubules - metabolism / Mitosis / multidisciplinary / Neoplasms - genetics / Neoplasms - metabolism / Ploidies / Science / Science (multidisciplinary) / Tumor cell lines / Tumor Suppressor Protein p53 - metabolism / Tumorigenesis