Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
Most cancer cells show abnormalities in chromosome number and structure (aneuploidy), which are attributed to chromosomal instability (a condition in which chromosome missegregation occurs at a high rate). Whether aneuploidy is a cause or consequence of cancer has long been debated, but recent studies have shown that aneuploidy promotes cancer progression and acquisition of drug resistance. For equal chromosome segregation, all pairs of replicated chromosomes (sister chromatids) must attach to microtubules extending from different spindle poles (biorientation), and to ensure this, there are mechanisms to correct erroneous attachments and to prevent chromosome segregation in the presence of erroneous attachments (spindle assembly checkpoint). Abnormalities in these mechanisms lead to chromosome missegregation, which results in micronucleus formation, causing rearrangement of chromosomes in the micronuclei (chromothripsis) and activation of the cGAS-STING pathway, an innate immune response. In this symposium, I will review the mechanisms of oncogenesis caused by chromosome missegregation. We have recently found that iterative motion of chromosomes on the spindle (oscillation) contributes to the equal segregation of chromosomes. Interestingly, chromosome oscillation is attenuated in cancer cells compared to normal cells, and I introduce this novel cause of chromosomal instability.
