Other
18 Authors
- Amoscato AA,
- Li Z,
- Dar HH,
- Duan S,
- Bayir H,
- Wang Z,
- Jiang X,
- Samovich SN,
- Tycko B,
- Zhang Z,
- Kon N,
- Kapralov AA,
- Kagan VE,
- Yang X,
- Stockwell BR,
- Tyurin VA,
- Gu W,
- Chen D
| First Author | Yang X | Year | 2024 |
| Journal | Cell Metab | Volume | 36 |
| Issue | 4 | Pages | 762-777.e9 |
| PubMed ID | 38309267 | Mgi Jnum | J:351979 |
| Mgi Id | MGI:7613886 | Doi | 10.1016/j.cmet.2024.01.006 |
| Citation | Yang X, et al. (2024) PHLDA2-mediated phosphatidic acid peroxidation triggers a distinct ferroptotic response during tumor suppression. Cell Metab |
| abstractText | Although the role of ferroptosis in killing tumor cells is well established, recent studies indicate that ferroptosis inducers also sabotage anti-tumor immunity by killing neutrophils and thus unexpectedly stimulate tumor growth, raising a serious issue about whether ferroptosis effectively suppresses tumor development in vivo. Through genome-wide CRISPR-Cas9 screenings, we discover a pleckstrin homology-like domain family A member 2 (PHLDA2)-mediated ferroptosis pathway that is neither ACSL4-dependent nor requires common ferroptosis inducers. PHLDA2-mediated ferroptosis acts through the peroxidation of phosphatidic acid (PA) upon high levels of reactive oxygen species (ROS). ROS-induced ferroptosis is critical for tumor growth in the absence of common ferroptosis inducers; strikingly, loss of PHLDA2 abrogates ROS-induced ferroptosis and promotes tumor growth but has no obvious effect in normal tissues in both immunodeficient and immunocompetent mouse tumor models. These data demonstrate that PHLDA2-mediated PA peroxidation triggers a distinct ferroptosis response critical for tumor suppression and reveal that PHLDA2-mediated ferroptosis occurs naturally in vivo without any treatment from ferroptosis inducers. |
