Activation of the p62‐Keap1‐NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells
Third Affiliated Hospital of Guangzhou Medical University · Guangzhou Medical University · +1 more institution
Abstract
UNLABELLED: Ferroptosis is a recently recognized form of regulated cell death caused by an iron-dependent accumulation of lipid reactive oxygen species. However, the molecular mechanisms regulating ferroptosis remain obscure. Here, we report that nuclear factor erythroid 2-related factor 2 (NRF2) plays a central role in protecting hepatocellular carcinoma (HCC) cells against ferroptosis. Upon exposure to ferroptosis-inducing compounds (e.g., erastin, sorafenib, and buthionine sulfoximine), p62 expression prevented NRF2 degradation and enhanced subsequent NRF2 nuclear accumulation through inactivation of Kelch-like ECH-associated protein 1. Additionally, nuclear NRF2 interacted with transcriptional coactivator…
Citation impact
- FWCI
- 24.92
- Percentile
- 100%
- References
- 40
Authors
7- XSXiaofang Sun
Third Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University
- ZOZhanhui Ou
Third Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University
- RCRuochan Chen
UPMC Hillman Cancer Center
- XNXiaohua Niu
Third Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University
- DCDe Chen
Third Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University
Topics & keywords
- KEAP1
- Gene knockdown
- Cancer research
- Transcription factor
- Sorafenib
- Chemistry
- Heme oxygenase
- Ferritin