The Dutch Cancer Society (KWF) has awarded a research grant to Geert Kops, to investigate the “Function and regulation of the fibrous corona of mitotic kinetochores in the protection of genome stability”. This research will lead to more insight into the mechanisms through which cells make sure that the number of chromosomes stays the same after each cell division, and how cancer can develop when this goes wrong.
Cells in most tumors are numerically and structurally aneuploid, which means that they contain an abnormal number of chromosomes and also structural changes to the chromosomes, such as translocations or deletions. These forms of aneuploidy develop due to mistakes in the segregation of chromosomes during mitosis, the last phase of cell division. These kinds of mistakes happen more often in cancer cells than in healthy cells. Many proteins and protein complexes are involved in the segregation of the chromosomes, one of which is the kinetochore.
Preliminary research by the Kops group has investigated a specific part of the mitotic kinetochore, the fibrous corona. This preliminary research has shown that the fibrous coronal may play a role in the surveillance mechanism that checks the segregation of chromosomes.
With the grant from the KWF, the Kops group can further investigate the importance of correct regulation of the fibrous corona in chromosome segregation. They will investigate various aspects of the fibrous corona using microscopy and proteomics, including its exact role in the surveillance mechanism, and compare healthy cells and cancer cells during cell division.The results of this research will generate more insight in how these mistakes in chromosome segregation are avoided in normal situations, and thereby also in the development of genomic instability in cancer. This may contribute to our knowledge about the origin of cancer.
Prof. dr. Geert Kops is group leader at the Hubrecht Instituut in Utrecht and professor of Molecular Tumor Cell Biologie at the University Medical Center Utrecht and Utrecht University.