ATF4 overexpression

A PUS7 consensus pseudouridylation site in the 3' untranslated region of ATF4 mRNA was crucial for the induction of ATF4 by cellular stress. These findings unveil a MYC-activated mRNA pseudouridylation program that mitigates cellular stress induced by MYC stimulation of proliferation and biomass production, suggesting that targeting PUS7 could be therapeutic strategy selectively against MYC-driven cancers.

In addition, DHA enhances the chemosensitivity of sorafenib on HCC in vivo and in vitro. These findings confirm that DHA induces ferroptosis of HCC via inhibiting ATF4-xCT pathway, thereby providing new drug options for the treatment of HCC.

Methyltransferase WTAP could regulate ATF4 expression, mediate cell apoptosis and endoplasmic reticulum stress, and promote H/R-induced myocardial cell injury.

ATF4 can represent a clinically useful biomarker to predict the overall survival rate, especially in patients with different subtypes of breast cancer. Provide certain guidance value for the development of targeted drugs or inhibitors targeting ATF4.

Tomatidine enhanced gemcitabine chemosensitivity in 3D ECM-hydrogels and in vivo. Tomatidine treatment was associated with induction of ferroptosis signaling validated by increased lipid peroxidation, mitochondrial biogenesis, and decreased GPX4 expression in PDAC cells. This study highlights a possible therapeutic approach utilizing a plant-derived metabolite, tomatidine, to target ATF4 activity in PDAC.