Superoxide dismutase promotes gastric tumorigenesis mediated by Helicobacter pylori and enhances resistance to 5-fluorouracil in gastric cancer
Summary: Helicobacter pylori (H. pylori) infection is the most common risk factor for gastric cancer (GC). The effect of the antioxidase manganese superoxide dismutase (SOD2) in gastric tumorigenesis remains unclear. We explored the molecular mechanisms of links between H. pylori, inflammation, and...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224027809 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832595735406706688 |
|---|---|
| author | Hongbing Fu Yu Zhang Yantao Duan Xin Zhang Jun Yao Dejun Yang Ziran Wei Zhenxin Zhu Jiapeng Xu Zunqi Hu Qing You Ronglin Yan Weijun Wang |
| author_facet | Hongbing Fu Yu Zhang Yantao Duan Xin Zhang Jun Yao Dejun Yang Ziran Wei Zhenxin Zhu Jiapeng Xu Zunqi Hu Qing You Ronglin Yan Weijun Wang |
| author_sort | Hongbing Fu |
| collection | DOAJ |
| description | Summary: Helicobacter pylori (H. pylori) infection is the most common risk factor for gastric cancer (GC). The effect of the antioxidase manganese superoxide dismutase (SOD2) in gastric tumorigenesis remains unclear. We explored the molecular mechanisms of links between H. pylori, inflammation, and SOD2 in GC. We found that SOD2 was upregulated in GC. GC patients with high SOD2 expression showed worse overall survival. H. pylori infection promoted SOD2 expression by transcriptionally activating the NF-κB signaling pathway. Knockdown of SOD2 led to increased levels of reactive oxygen species and oxidative stress in response to H. pylori infection. Our research demonstrates that SOD2 can serve as an inhibitor of ferroptosis by activating AKT, and stabilizing GPX4 protein, which subsequently induces 5-fluorouracil resistance. These findings reveal a mechanism whereby H. pylori can promote gastric carcinogenesis by activating the NF-κB/SOD2/AKT/GPX4 pathway, leading to the inhibition of ferroptosis. This may provide a promising therapeutic target for GC. |
| format | Article |
| id | doaj-art-156867ecee734425916dd7ea57ade769 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-156867ecee734425916dd7ea57ade7692025-01-18T05:05:03ZengElsevieriScience2589-00422025-02-01282111553Superoxide dismutase promotes gastric tumorigenesis mediated by Helicobacter pylori and enhances resistance to 5-fluorouracil in gastric cancerHongbing Fu0Yu Zhang1Yantao Duan2Xin Zhang3Jun Yao4Dejun Yang5Ziran Wei6Zhenxin Zhu7Jiapeng Xu8Zunqi Hu9Qing You10Ronglin Yan11Weijun Wang12Department of Gastrointestinal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Gastrointestinal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, China; Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Gastrointestinal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Gastrointestinal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Gastrointestinal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Gastrointestinal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Gastrointestinal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Gastrointestinal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Gastrointestinal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Gastrointestinal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, ChinaDepartment of Gastrointestinal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, China; Corresponding authorDepartment of Gastrointestinal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, China; Corresponding authorSummary: Helicobacter pylori (H. pylori) infection is the most common risk factor for gastric cancer (GC). The effect of the antioxidase manganese superoxide dismutase (SOD2) in gastric tumorigenesis remains unclear. We explored the molecular mechanisms of links between H. pylori, inflammation, and SOD2 in GC. We found that SOD2 was upregulated in GC. GC patients with high SOD2 expression showed worse overall survival. H. pylori infection promoted SOD2 expression by transcriptionally activating the NF-κB signaling pathway. Knockdown of SOD2 led to increased levels of reactive oxygen species and oxidative stress in response to H. pylori infection. Our research demonstrates that SOD2 can serve as an inhibitor of ferroptosis by activating AKT, and stabilizing GPX4 protein, which subsequently induces 5-fluorouracil resistance. These findings reveal a mechanism whereby H. pylori can promote gastric carcinogenesis by activating the NF-κB/SOD2/AKT/GPX4 pathway, leading to the inhibition of ferroptosis. This may provide a promising therapeutic target for GC.http://www.sciencedirect.com/science/article/pii/S2589004224027809Molecular biologyCancer |
| spellingShingle | Hongbing Fu Yu Zhang Yantao Duan Xin Zhang Jun Yao Dejun Yang Ziran Wei Zhenxin Zhu Jiapeng Xu Zunqi Hu Qing You Ronglin Yan Weijun Wang Superoxide dismutase promotes gastric tumorigenesis mediated by Helicobacter pylori and enhances resistance to 5-fluorouracil in gastric cancer iScience Molecular biology Cancer |
| title | Superoxide dismutase promotes gastric tumorigenesis mediated by Helicobacter pylori and enhances resistance to 5-fluorouracil in gastric cancer |
| title_full | Superoxide dismutase promotes gastric tumorigenesis mediated by Helicobacter pylori and enhances resistance to 5-fluorouracil in gastric cancer |
| title_fullStr | Superoxide dismutase promotes gastric tumorigenesis mediated by Helicobacter pylori and enhances resistance to 5-fluorouracil in gastric cancer |
| title_full_unstemmed | Superoxide dismutase promotes gastric tumorigenesis mediated by Helicobacter pylori and enhances resistance to 5-fluorouracil in gastric cancer |
| title_short | Superoxide dismutase promotes gastric tumorigenesis mediated by Helicobacter pylori and enhances resistance to 5-fluorouracil in gastric cancer |
| title_sort | superoxide dismutase promotes gastric tumorigenesis mediated by helicobacter pylori and enhances resistance to 5 fluorouracil in gastric cancer |
| topic | Molecular biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224027809 |
| work_keys_str_mv | AT hongbingfu superoxidedismutasepromotesgastrictumorigenesismediatedbyhelicobacterpyloriandenhancesresistanceto5fluorouracilingastriccancer AT yuzhang superoxidedismutasepromotesgastrictumorigenesismediatedbyhelicobacterpyloriandenhancesresistanceto5fluorouracilingastriccancer AT yantaoduan superoxidedismutasepromotesgastrictumorigenesismediatedbyhelicobacterpyloriandenhancesresistanceto5fluorouracilingastriccancer AT xinzhang superoxidedismutasepromotesgastrictumorigenesismediatedbyhelicobacterpyloriandenhancesresistanceto5fluorouracilingastriccancer AT junyao superoxidedismutasepromotesgastrictumorigenesismediatedbyhelicobacterpyloriandenhancesresistanceto5fluorouracilingastriccancer AT dejunyang superoxidedismutasepromotesgastrictumorigenesismediatedbyhelicobacterpyloriandenhancesresistanceto5fluorouracilingastriccancer AT ziranwei superoxidedismutasepromotesgastrictumorigenesismediatedbyhelicobacterpyloriandenhancesresistanceto5fluorouracilingastriccancer AT zhenxinzhu superoxidedismutasepromotesgastrictumorigenesismediatedbyhelicobacterpyloriandenhancesresistanceto5fluorouracilingastriccancer AT jiapengxu superoxidedismutasepromotesgastrictumorigenesismediatedbyhelicobacterpyloriandenhancesresistanceto5fluorouracilingastriccancer AT zunqihu superoxidedismutasepromotesgastrictumorigenesismediatedbyhelicobacterpyloriandenhancesresistanceto5fluorouracilingastriccancer AT qingyou superoxidedismutasepromotesgastrictumorigenesismediatedbyhelicobacterpyloriandenhancesresistanceto5fluorouracilingastriccancer AT ronglinyan superoxidedismutasepromotesgastrictumorigenesismediatedbyhelicobacterpyloriandenhancesresistanceto5fluorouracilingastriccancer AT weijunwang superoxidedismutasepromotesgastrictumorigenesismediatedbyhelicobacterpyloriandenhancesresistanceto5fluorouracilingastriccancer |