Year: 2020
Type: dissertation
Abstract: Chromosomal Instability (CIN) and associated aneuploidy are salient\n\t\t\t\t features of the majority of human solid tumors. In the Drosophila\n\t\t\t\t epithelial model of CIN, the generation of highly aneuploid\n\t\t\t\t karyotypes drive cell delamination and c-Jun N-terminal Kinase\n\t\t\t\t (JNK) dependent cell death. Aneuploidy associated generation of\n\t\t\t\t Reactive Oxygen Species (ROS) plays a key role in the activation of\n\t\t\t\t JNK. When delaminating cells are maintained in the tissue by\n\t\t\t\t apoptosis inhibition, aberrant karyotypes promote a cell-autonomous\n\t\t\t\t malignant behavior. Here we have dissected the molecular\n\t\t\t\t mechanisms underlying aneuploidy-induced ROS production and\n\t\t\t\t cell delamination. On one hand, we have shown that aneuploidy\n\t\t\t\t associated proteotoxic stress is being sensed and activates the major\n\t\t\t\t protein quality control mechanisms in a cell. On the other hand,\n\t\t\t\t mitochondria act as signaling centers as well as major sensors of the\n\t\t\t\t unbalanced proteome in CIN tissues. Aneuploidy associated\n\t\t\t\t proteotoxic stress leads to mitochondrial dysfunction and ROS\n\t\t\t\t production, which further drives cell delamination as well as JNK\n\t\t\t\t activation in CIN tissues.
Author: Jery Joy
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3014875842