"Length matters: Causes and consequences of centriole length deregulation in cancer"

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Publications

Building the right centriole for each cell type

Publication . Loncarek, Jadranka; Bettencourt-Dias, Mónica

The centriole is a multifunctional structure that organizes centrosomes and cilia and is important for cell signaling, cell cycle progression, polarity, and motility. Defects in centriole number and structure are associated with human diseases including cancer and ciliopathies. Discovery of the centriole dates back to the 19th century. However, recent advances in genetic and biochemical tools, development of high-resolution microscopy, and identification of centriole components have accelerated our understanding of its assembly, function, evolution, and its role in human disease. The centriole is an evolutionarily conserved structure built from highly conserved proteins and is present in all branches of the eukaryotic tree of life. However, centriole number, size, and organization varies among different organisms and even cell types within a single organism, reflecting its cell type-specialized functions. In this review, we provide an overview of our current understanding of centriole biogenesis and how variations around the same theme generate alternatives for centriole formation and function.

2017-12-28Review

Open access

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

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

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.

2018-03-28Journal article

Open access