By Daniel Walocha ‘19
Oncogene overexpression will lead to cancer phenotypes that can accumulate cytotoxic metabolites, reactive oxygen species (ROS), and other apoptosis-inducing factors in the cell. It is therefore necessary for the cancerous cell to eliminate the apoptosis-inducing factors or suppress apoptosis altogether. Dr. Megan Romeo et al. from Richland College has detected a mechanism in which a cooperative pathway utilizes a cellular protein to avoid cellular apoptosis or senescence, thereby promoting the tumorigenic properties of the cell.
Dr. Romeo et al. worked with virally transformed human T-cell leukemia type 1 in clinical isolates to exhibit the induction of Tp53-induced glycolysis and apoptosis regulator (TIGAR) and its role in c-myc oncogene expression. C-myc is a gene that encodes for proteins involved in mitogenic signaling and transcription factors involved in cell growth, so overexpression has been linked to cancer.
The Warburg Effect states that cancer cells preferentially use glycolysis for their ATP needs, so the research team measured tp53-mediated TIGAR induction in the T-cell leukemia type 1 cells using western blots and fluorescent labeling to observe how TIGAR eliminates harmful intermediates that would lead to cell death. It was found that Tp53, which was acetylated on lysine residue 120, induced TIGAR induction. TIGAR induction was further shown to reduce cytotoxic intermediates and reactive oxygen species.
The study identifies an important therapeutic target in targeting T-cell leukemia type 1, which overexpresses TIGAR to avoid apoptosis. Future research should be aimed to further elaborate on the mechanism by which Tp53 induces TIGAR overexpression and look to intervene in its pathway.
- M. Romeo, et al. The human T-cell leukemia virus type-1 p30II protein activates p53 and induces the TIGAR and suppresses oncogene-induced oxidative stress during viral carcinogenesis. Virology 518, 103-115 (2018). doi: 10.1016/j.virol.2018.02.010.
- Image retrieved from: http://www.pnas.org/content/103/41/15056