Table 5.
Posttranslational modification of Ferroptosis by GlcNAcylation in cancer
| Cancer | Modification | Targets | Enzyme | Biological functions | Ref |
|---|---|---|---|---|---|
| HCC | O-GlcNAcylation | c-Jun | - | O-GlcNAcylated c-Jun antagonizes ferroptosis via inhibiting GSH synthesis in liver cancer. Erastin specifically inhibited c-Jun O-GlcNAcylation in liver cancer and further suppressed the related cancer-promoting function of c-Jun. Overexpression of O-GlcNAcylated c-Jun conversely repressed ferroptosis via stimulating GSH synthesis through boosting the transcription of PSAT1 and CBS. | 205 |
| HCC | O-GlcNAcylation | YAP | - | O-GlcNAcylated YAP mediates the ferroptosis sensitivity through transcriptional elevation of TFRC in HCC cells | 206 |
| Pancreatic cancer | O-GlcNAcylation | ZEB1 | - | O-GlcNAcylation of ZEB1 facilitated mesenchymal pancreatic cancer cell ferroptosis. High glucose increased O-GlcNAcylation of ZEB1, transcriptionly inducing FASN and FADS2, thereby resulting in ferroptosisin mesenchymal pancreatic cancer cells. | 207 |
| OC | O-GlcNAcylation | EGFR | GALNT14 | GALNT14 is significantly upregulated in ovarian cancer. Downregulation of GALNT14 significantly inhibits both apoptosis and ferroptosis of ovarian cancer cells. Downregulation of GALNT14 suppresses the activity of the mTOR pathway through modifying O-glycosylation of EGFR. Finally, an additive effect promoting cell death occurs with a combination of an mTOR inhibitor and cisplatin. | 208 |
| BC | N-GlcNAcylation | SREBP1 | ALG3 | Inhibition of ALG3 lead to N-linked glycosylation deficiency-mediated ferroptosis to boost anti-PD1 immunotherapy. | 209 |
| Osteosarcoma | O-GlcNAcylation | FTH | - | Inhibition of O-GlcNAcylation promoted ferritinophagy, resulting in the accumulation of labile iron and rendering the cell more sensitive to ferroptosis. de-O-GlcNAcylation of the FTH at S179 promoted its interaction with NCOA4, the ferritinophagy receptor, thereby accumulating labile iron for ferroptosis. | 210 |
ALG3 alpha 1,3-mannosyltransferase, BC breast cancer, CBS cystathionine-beta-synthase, EGFR epidermal growth factor receptor, FADS2 fatty acid desaturase 2, FASN fatty acid synthase, GALNT14 N-Acetylgalactosaminyltransferase-14, FTH ferritin heavy chain, OC Ovarian cancer, PSAT1 phosphoserine aminotransferases 1, TFRC transferrin receptor