Glutamine synthetase shields triple-negative breast cancer cells from ferroptosis in metastasis triggered by glutamine deprivation.

ABSTRACT:

Background

Epithelial-mesenchymal transition (EMT) in cancer cell metastasis involves complicated metabolic plasticity to survive the highly challenging environment, such as oxidative stress, after subsequent circulation in the bloodstream. Glutamine synthetase (GS) is an enzyme that converts glutamate and ammonia to glutamine (Gln) during Gln deprivation stress. This study revealed for the first time that GS plays an important role in protecting triple-negative breast cancer (TNBC) cells from ferroptosis during Gln deprivation-induced EMT, namely ferroptosis-resistant EMT (FR-EMT).

Methods

To better understand this finding, we focused on the mechanism of GS-mediated FR-EMT in TNBC through transcriptomic analysis and murine metastasis modeling.

Results

This study spec

SUBMITTER: Yang Z 

PROVIDER: S-EPMC12465765 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature