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Review
. 2023 Sep 27;24(19):14614.
doi: 10.3390/ijms241914614.

Regulation of Ferroptosis in Lung Adenocarcinoma

Xiangyun Wei  1 , Xiaohe Li  1 , Shuming Hu  1 , Jinke Cheng  1 , Rong Cai  1
Affiliations
Review

Regulation of Ferroptosis in Lung Adenocarcinoma

Xiangyun Wei et al. Int J Mol Sci. .

Abstract

Lung adenocarcinoma (LUAD) is the most common lung cancer, which accounts for about 35-40% of all lung cancer patients. Despite therapeutic advancements in recent years, the overall survival time of LUAD patients still remains poor, especially KRAS mutant LUAD. Therefore, it is necessary to further explore novel targets and drugs to improve the prognos is for LUAD. Ferroptosis, an iron-dependent regulated cell death (RCD) caused by lipid peroxidation, has attracted much attention recently as an alternative target for apoptosis in LUAD therapy. Ferroptosis has been found to be closely related to LUAD at every stage, including initiation, proliferation, and progression. In this review, we will provide a comprehensive overview of ferroptosis mechanisms, its regulation in LUAD, and the application of targeting ferroptosis for LUAD therapy.

Keywords: ferroptosis; lung adenocarcinoma; regulation; therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Ferroptosis in LUAD tumorigenesis and progression. a. Ferroptosis in LUAD initiation; b. Ferroptosis in LUAD proliferation. RRM2, ribonucleotide reductase subunit M2; CCT3, chaperonin containing TCP1 subunit 3; NFS1, nitrogen fixation 1; ZEB1, zinc finger E-box binding homeobox 1; Fer-1, ferrostatin-1; TKI, tyrosine kinase inhibitor. Created with BioRender.com.
Figure 2
Figure 2
Master transcriptional regulators of ferroptosis in LUAD. (A) NFE2L2 is a crucial anti-ferroptotic transcription factor in LUAD cells, as it regulates multiple genes involved in antioxidant defense. The expression of NFE2L2 is primarily controlled by ubiquitination and proteasome-mediated degradation. Multiple E3 ubiquitin ligases or de-ubiquitinating enzymes regulate the sensitivity to ferroptosis by controlling the expression of NFE2L2 in LUAD cells. (B) TP53 inhibits ferroptosis and LUAD progression by suppressing the expression of SLC7A11 and GPX4. Acetylation is very important in the regulation of its function in ferroptosis because it increases the stability of the p53 protein. (C) YAP1 plays a dual role in ferroptosis, depending on the expression of its target genes. The O-GlcNAcylation of YAP1, which is mediated by O-GlcNAc, enhances the activity of YAP1 and its transcriptional ability. In LUAD cells, the sensitivity to ferroptosis can be regulated by controlling its upstream ADCY/PKA/HBP axis. (D) ARNTL2 promotes ferroptosis by promoting the expression of ACOT7, a MUFA synthesis-related enzyme. (E) CREB1 inhibits while KLF11 promotes ferroptosis by binding to the promoter of GPX4. Created with BioRender.com.
See this image and copyright information in PMC

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