Towards understanding the mechanism of tumorigenesis caused by centrosome dysfunction
Authors: Chaitali Khan; Nasser Rusan
Affiliation: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
Keywords: h. tumorigenesis; g. asymmetric cell division
Centrosome dysfunction is prevalent in many types of cancers; however, the mechanistic understanding by which centrosome defects cause cancer is still not very clear. Some studies have shown that centrosome amplification causes cancer by inducing mitotic errors and genomic instability. Other studies link centrosome dysfunction and tumorigenesis to the activation of a cellular stress response. Centrosome dysfunction can also lead to cancer by disrupting asymmetric stem cell division, which leads to errors in daughter cell fate. In Drosophila, genetic perturbations that disrupt Drosophila neural stem cells (NSC) asymmetric division, including centrosome mutations, give rise to tumors. Some of these mutations form tumors in the larva brain while others give rise to tumors upon transplanting NSC into the adult fly abdomen by an allograft method. We are using the allograft method to investigate tumorigenesis caused by compromised centrosome function in asymmetric stem cell division. Specifically, we are testing how does abnormal centrosomes affect the stem cell polarity and cell fate specification, genomic instability and how does this causes tumorigenesis of NSCs. Additionally, we are investigating the role of cellular stress response triggered due to dysfunctional centrsomes and its cooperation with tumorigenic signaling pathways in a cell autonomous or non autonomous manner. I will be discussing our findings addressing these questions.