Scientists say they have discovered critical features of cancer cells that may help clinicians better fight the disease. The researchers found that the number and size of centrioles are increased in the most aggressive subtypes of cancer. Their study (“Over-Elongation of Centrioles in Cancer Promotes Centriole Amplification and Chromosome Missegregation”) appears in Nature Communications.
“Centrosomes are the major microtubule organising centers 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 analyze 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,” write the investigators.
“…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 is a diverse disease, with some tumors being more aggressive and more resistant to chemotherapy than others. Clinicians are eager to find novel diagnostic, prognostic, and treatment tools that will allow them to predict outcomes and treat patients in a more personalized way. The team believes their findings may contribute to this process.
Centrioles have been called the cell’s brain as they play crucial roles in cell multiplication, movement, and communication. Their number and size are highly controlled in normal cells. Since their discovery, more than one century ago, it has been proposed that an abnormal increase in the number of these structures may induce cancer.
Mónica Bettencourt-Dias, Ph.D., from the Instituto Gulbenkian de Ciência (IGC, Portugal), and colleagues investigated the incidence of centriole abnormalities in human cancer cells. The researchers analyzed a panel of 60 human cancer lines originating from nine distinct tissues. Their results showed that cancer cells often have extra and longer centrioles, which are absent in normal cells. Importantly, the research team observed that supernumerary centrioles are more prevalent in aggressive breast—e.g., triple-negative—and colon cancer. Also, the team discovered that longer centrioles are excessively active, which perturbs cell division and could favor cancer formation.
“Our data confirm that the deregulated number and size of centrioles inside cells is associated with malignant features. This finding may help establishing centriole properties as a way of classifying tumors in order to establish prognosis and predict treatment response,” says Gaëlle Marteil, Ph.D., first author of the study and researcher at the Bettencourt-Dias laboratory.
“The cell lines that we analyzed are already well characterized in terms of genetic changes and resistance to therapeutics. We are pursuing our studies in collaboration with the teams of Nuno Barbosa-Morais, Ph.D., at the Instituto de Medicina Molecular, in Lisbon, and Joana Paredes, Ph.D., at I3S, in Porto, to explore new mechanisms and therapeutics that could target centrioles in cancer,” adds Dr. Bettencourt-Dias.