ArticleOncotarget2015
Hydrogen peroxide mediates hyperglycemia-induced invasive activity via ERK and p38 MAPK in human pancreatic cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Metabolic Syndrome and Pancreatic Cancer: Linking Insulin Resistance, Inflammation, and Carcinogenesis.Diagnostics (Basel, Switzerland) · 2026Review
- Estradiol Reshapes Cell-Type-Dependent Basal Redox Set-Points in Colorectal Carcinoma Cells.Biomedicines · 2026Article
- Impact of poorly controlled type II diabetes mellitus on chemoresistance in colorectal cancer.World journal of gastroenterology · 2025Review
- Balanced Duality: HInternational journal of molecular sciences · 2024Review
- Assessing the Link between Diabetic Metabolic Dysregulation and Breast Cancer Progression.International journal of molecular sciences · 2023Article
- Antioxidant and Anti-Tumor Effects of Dietary Vitamins A, C, and E.Antioxidants (Basel, Switzerland) · 2023Review
- Differential effects of glucose and N-acetylglucosamine on genome instability.American journal of cancer research · 2022Article
- Novel role of xanthine oxidase-dependent HRedox biology · 2021Article
- High glucose: an emerging association between diabetes mellitus and cancer progression.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Antimetastatic Effects of Curcumin in Oral and Gastrointestinal Cancers.Frontiers in pharmacology · 2021Review
- Hyperglycemia during Adjuvant Chemotherapy as a Prognostic Factor in Breast Cancer Patients without Diabetes.Journal of breast cancer · 2020Article
- The roles of curcumin in regulating the tumor immunosuppressive microenvironment.Oncology letters · 2020Review
- Identify potential clinical significance of long noncoding RNA forkhead box P4 antisense RNA 1 in patients with early stage pancreatic ductal adenocarcinoma.Cancer medicine · 2020Article
- Hyperglycemia enhances pancreatic cancer progression accompanied by elevations in phosphorylated STAT3 and MYC levels.PloS one · 2020Article
- Effects of hyperglycemia on the progression of tumor diseases.Journal of experimental & clinical cancer research : CR · 2019Review
- Hydrogen peroxide-induced mitophagy contributes to laryngeal cancer cells survival via the upregulation of FUNDC1.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Article
- ZO-1 protein is required for hydrogen peroxide to increase MDCK cell paracellular permeability in an ERK 1/2-dependent manner.American journal of physiology. Cell physiology · 2018Article
- High Glucose-Induced ROS Production Stimulates Proliferation of Pancreatic Cancer via Inactivating the JNK Pathway.Oxidative medicine and cellular longevity · 2018Article
- Hyperglycemia aggravates microenvironment hypoxia and promotes the metastatic ability of pancreatic cancer.Computational and structural biotechnology journal · 2018Article
- Effect of antioxidant of bamboo leaves on gene expression associated with mouse embryonic fibroblast reproduction and embryonic development.Molecular medicine reports · 2017Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetes mellitus and pancreatic cancer are intimately related, as approximately 85% of pancreatic cancer patients suffer from glucose intolerance or even diabetes. In this study, we evaluate the underlying mechanism by which hyperglycemia modulates the invasive potential of cancer cells and contributes to their enhanced metastatic behavior. Here we show that hyperglycemia increases the hydrogen peroxide (H2O2) concentration through up-regulation of manganese superoxide dismutase (SOD2) expression, which further activates the ERK and p38 MAPK pathways, as well as the transcription factors NF-κB and AP-1, in a time-dependent manner. The invasion of pancreatic cancer cells resulting from the activation of the H2O2/MAPK axis under high glucose conditions is effectively inhibited by PD 98059 (ERK inhibitor), SB 203580 (p38 MAPK inhibitor), polyethylene glycol-conjugated catalase (PEG-CAT), or the siRNA specific to SOD2. In addition, streptozotocin-treated diabetic nude mice exhibit a stronger tumor invasive ability in renal capsule xenografts which could be suppressed by PEG-CAT treatment. Furthermore, the integrated optical density (IOD) of SOD2 and uPA stainings is higher in the tumor tissues of pancreatic cancer patients with diabetes compared with pancreatic cancer patients with euglycemia. Taken together, our results demonstrate that hyperglycemia enhances cell invasive ability through the SOD2/H2O2/MAPK axis in human pancreatic cancer. Thus, SOD2/H2O2/MAPK axis may represent a promising therapeutic target for pancreatic cancer patients combined with diabetes mellitus.
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