Understanding GPX4 Function in Cancer Cell Survival [Feb. 25, 2025]

Understanding GPX4 Function in Cancer Cell Survival [Feb. 25, 2025] 

Previous Science Note

GPX4, a selenoprotein, inhibits lipid oxidation and protects cancer cells from oxidative damage and ferroptosis. Targeting GPX4 has emerged as a promising strategy, offering new avenues for cancer treatment. This Science Note introduces recent research papers on cancer and GPX4.

Breast cancer secretes anti-ferroptotic MUFAs and depends on selenoprotein synthesis for metastasis 
Tobias Ackermann, et. al., EMBO Mol. Med., 2024.

Triple-negative breast cancer (TNBC) cells secrete anti-ferroptotic MUFAs via SCD, however, during metastasis, low SCD levels make them dependent on GPX4. Thus, inhibition of selenocysteine synthesis induces ferroptosis, which impairs metastasis.

Highlighted technique: Measurement of lipid peroxidation is a key indicator of ferroptosis and has been widely reported in various research publications. C11 BODIPY is commonly used to detect lipid peroxidation, while Liperfluo, with its higher specificity for lipid peroxides, serves as a valuable tool for ferroptosis research.

Dysregulated cholesterol homeostasis results in resistance to ferroptosis increasing tumorigenicity and metastasis in cancer
Wen Liu, et. al., Nature Communications, 2021.

Summary Lipid accumulation in hypercholesterolemia and dyslipidemia creates metabolic stress that necessitates GPX4 expression, promoting ferroptosis resistance and enhancing tumorigenicity and metastasis in cancer.

Highlighted technique: In vivo experiments are essential for assessing cancer metastasis, but they are time-consuming. For rapid evaluation, Migration Assays such as those described in this paper can be useful.

PRDX6 dictates ferroptosis sensitivity by directing cellular selenium utilization
Junya Ito, et. al., Molecular Cell, 2024.

GPX4 prevents ferroptosis by reducing phospholipid hydroperoxides, while PRDX6 supports GPX4 by increasing selenium utilization, and its loss decreases GPX4 levels, increasing cancer cell sensitivity to ferroptosis.

Highlighted technique: This paper describes an affinity purification method for GPX4 analysis. A more detailed purification and evaluation method can be found in the authors' report in Cell Reports Methods.

Related Techniques (click to open/close)
Application Note (click to open/close)
  > Erastin-Induced Ferroptosis: Evaluating Intracellular Uptake and Redox Balance
 

Product Classification

Product Classification