Year: 2024
Type: dissertation
Abstract: 2-aminoethanethiol dioxygenase (ADO) is a mammalian thiol dioxygenase that metabolizes cysteamine to produce hypotaurine. Little is known about the (patho)physiological role(s) of ADO. Recently, our lab discovered that high ADO expression is associated with poor survival in patients with liver cancer, and ADO depletion led to a substantial decrease in liver cancer cell proliferation and survival. In this thesis, we hypothesized that ADO depletion inhibits liver cancer cell proliferation and survival through metabolic alterations. We assessed the metabolic changes upon ADO depletion and revealed dysregulation of polyamines. We demonstrate that regulation of polyamines through ADO is important for liver cancer cells to restrain levels of reactive oxygen species (ROS), and to support cell proliferation and clonogenic survival. This work provides novel insight into the functional metabolic role of ADO, and how its regulation of the liver cancer metabolome is essential for promoting the growth and survival of liver cancer cells.
Source: TSpace (University of Toronto)
Author: Pyo, Andrea Hye An
Institution: University of Toronto
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7132941497