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Ferroptosis in liver cancer: a key role of post-translational modifications
Ying Xu1, Zhiyao Xing1, Ruaa Abdalla Ibrahim Suliman1
1School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.
Abstract:
Ferroptosis is an emerging form of regulated cell death in an oxidative stress- and iron-dependent manner, primarily induced by the over-production of reactive oxygen species (ROS). Manipulation of ferroptosis has been considered a promising therapeutic approach to inhibit liver tumor growth. Nevertheless, the development of resistance to ferroptosis in liver cancer poses a significant challenge in cancer treatment. Post-translational modifications (PTMs) are crucial enzymatic catalytic reactions that covalently regulate protein conformation, stability and cellular activities. Additionally, PTMs play pivotal roles in various biological processes and divergent programmed cell death, including ferroptosis. Importantly, key PTMs regulators involved in ferroptosis have been identified as potential targets for cancer therapy. PTMs function of two proteins, SLC7A11, GPX4 involved in ferroptosis resistance have been extensively investigated in recent years. This review will summarize the roles of PTMs in ferroptosis-related proteins in hepatocellular carcinoma (HCC) treatment.
Insights
Ferroptosis, a cell death pathway, is key to inhibiting liver tumors. Understanding post-translational modifications (PTMs) in ferroptosis resistance is crucial for developing effective hepatocellular carcinoma (HCC) treatments.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Ferroptosis is an iron-dependent regulated cell death pathway.
- Over-production of reactive oxygen species (ROS) induces ferroptosis.
- Ferroptosis manipulation is a promising strategy for liver tumor growth inhibition.
Purpose of the Study:
- To review the roles of post-translational modifications (PTMs) in ferroptosis.
- To explore PTMs' impact on ferroptosis resistance in hepatocellular carcinoma (HCC).
- To identify PTMs as potential therapeutic targets for HCC treatment.
Main Methods:
- Literature review focusing on PTMs and ferroptosis.
- Analysis of PTMs' regulatory roles in ferroptosis-related proteins.
- Investigation of PTMs' involvement in ferroptosis resistance mechanisms.
Main Results:
- PTMs critically regulate protein function, stability, and cellular activities.
- PTMs are involved in various programmed cell death pathways, including ferroptosis.
- Key PTMs regulators are identified as potential therapeutic targets.
Conclusions:
- PTMs play a significant role in regulating ferroptosis.
- Understanding PTMs in ferroptosis resistance is vital for HCC treatment strategies.
- Targeting PTMs offers a promising avenue for overcoming ferroptosis resistance in HCC.
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