Back to Search
Start Over
Mild Oxidative Stress Reduces NRF2 SUMOylation to Promote Kras / Lkb1 / Keap1 Mutant Lung Adenocarcinoma Cell Migration and Invasion.
- Source :
-
Oxidative medicine and cellular longevity [Oxid Med Cell Longev] 2020 Nov 24; Vol. 2020, pp. 6240125. Date of Electronic Publication: 2020 Nov 24 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- Nuclear factor erythroid 2-related factor 2 (NRF2) is a crucial transcription factor for cell adaptation and defense against oxidative stress. NRF2 activation confers Kras / Lkb1 / Keap1 (KLK) mutant tumor cells with greater resistance to oxidative insults. We previously reported that SUMOylation at lysine residue 110 is important for the ability of NRF2 to promote reactive oxygen species (ROS) clearance in hepatocellular carcinoma. In this study, we investigated whether SUMOylation is necessary for the ability of NRF2 to inhibit KLK lung adenocarcinoma (LUAD) cell migration and invasion. Our experiments showed that mild oxidative stress reduced NRF2 SUMOylation, which promoted KLK LUAD cell migration and invasion. Mechanistically, NRF2 SUMOylation increased the antioxidant ability of NRF2 and reduced cellular ROS levels, mainly by transcriptionally activating Cat in KLK LUAD cells. With reduced NRF2 SUMOylation, increased ROS acted as signaling molecules to activate the JNK/c-Jun axis, which enhanced cell mobility and cell adhesion, to promote LUAD cell migration and invasion. Taken together, the results of this study reveal a novel signaling process in which reduced NRF2 SUMOylation permits increased KLK LUAD cell migration and invasion under mild oxidative stress.<br />Competing Interests: The authors declare no competing interest.<br /> (Copyright © 2020 Jiaqian Xu et al.)
- Subjects :
- Adenocarcinoma of Lung genetics
Adenocarcinoma of Lung metabolism
Antioxidants metabolism
Carcinoma, Hepatocellular metabolism
Cell Line, Tumor
Cell Movement genetics
Humans
Kelch-Like ECH-Associated Protein 1 genetics
Liver Neoplasms metabolism
Lung Neoplasms genetics
Lung Neoplasms pathology
NF-E2-Related Factor 2 genetics
Oxidative Stress drug effects
Proto-Oncogene Proteins p21(ras) genetics
Reactive Oxygen Species metabolism
Sumoylation drug effects
Cell Movement physiology
Kelch-Like ECH-Associated Protein 1 metabolism
Lung Neoplasms metabolism
NF-E2-Related Factor 2 metabolism
Oxidative Stress physiology
Proto-Oncogene Proteins p21(ras) metabolism
Sumoylation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1942-0994
- Volume :
- 2020
- Database :
- MEDLINE
- Journal :
- Oxidative medicine and cellular longevity
- Publication Type :
- Academic Journal
- Accession number :
- 33299528
- Full Text :
- https://doi.org/10.1155/2020/6240125