Identifying causes and consequences of centrosome amplification in cancer

项目摘要/摘要

PROJECT SUMMARY / ABSTRACT Cancer is the second leading cause of death in the U.S., and novel therapeutics are of great need. Centrosomes are cellular microtubule organizing centers that are important for the faithful division of chromosomes during mitosis and are commonly dysregulated in cancer. Most human tumors have cells with centrosome amplification, or an abnormally elevated number of centrosomes. As a result of centrosome amplification, cancer cells can undergo asymmetric cell division, leading to chromosomal instability and aneuploidy, which is a source of genetic diversity that allows cancer to evolve and evade therapies. However, it is unclear how centrosome amplification arises, how it affects patient outcomes, and how it affects migration and metastatic potential. The overarching goal of this proposed research is to understand how centrosomes are dysregulated in cancer and to investigate the subsequent cellular and clinical consequences. The research proposed herein will enhance our knowledge of centrosome amplification in cancer, especially cancer cell division and migration, and potentially identify novel ways to target cancer cells with centrosome amplification.