ArticlePloS one2020
Hyperglycemia enhances pancreatic cancer progression accompanied by elevations in phosphorylated STAT3 and MYC levels.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Preoperative Glucose-to-Albumin Ratio as a Prognostic Marker for Survival in Pancreatic Cancer Patients Undergoing Pancreatectomy.Cancer medicine · 2026Article
- Impact of good glycemic control on survival of pancreatic ductal adenocarcinoma with diabetes mellitus.BMC gastroenterology · 2026Article
- Pancreatic Cystic Neoplasm Risk Among Individuals With Diabetes.JAMA network open · 2026Article
- Metabolic reprogramming in diabetes and cancer: the role of PI3K/AKT/mTOR and beyond.American journal of cancer research · 2026Review
- Prediction of Pancreatic Cancer Risk in Patients with New-Onset Diabetes.Visceral medicine · 2025Review
- Role of diabetes-related inflammation in pancreatic cancer evaluated by aptamer-based detection of circulating tumor cells in a streptozotocin-induced Panc02-transplanted murine model.Annals of hepato-biliary-pancreatic surgery · 2025Article
- The Role of Inflammation in Cancer: Mechanisms of Tumor Initiation, Progression, and Metastasis.Cells · 2025Review
- Increased autophagy activity suppresses hyperglycemia-related colorectal cancer tumorigenesis bothAmerican journal of cancer research · 2025Article
- Exocrine Pancreas in Type 1 and Type 2 Diabetes: Different Patterns of Fibrosis, Metaplasia, Angiopathy, and Adiposity.Diabetes · 2024Article
- Bidirectional relationship between pancreatic cancer and diabetes mellitus: a comprehensive literature review.Annals of medicine and surgery (2012) · 2024Review
- The serum tenascin C level is a marker of metabolic disorder-related inflammation affecting pancreatic cancer prognosis.Scientific reports · 2024Article
- Strengthening the Evidence for a Causal Link between Type 2 Diabetes Mellitus and Pancreatic Cancer: Insights from Two-Sample and Multivariable Mendelian Randomization.International journal of molecular sciences · 2024Article
- MYC-mediated resistance to trametinib and HCQ in PDAC is overcome by CDK4/6 and lysosomal inhibition.The Journal of experimental medicine · 2023Article
- Target c-Myc to treat pancreatic cancer.Cancer biology & therapy · 2022Article
- Pentraxin 3 is an adipose tissue-related serum marker for pancreatic cancer cachexia predicting subsequent muscle mass and visceral fat loss.Cancer science · 2022Article
- B7H6 Serves as a Negative Prognostic Marker and an Immune Modulator in Human Pancreatic Cancer.Frontiers in oncology · 2022Article
- Docosahexaenoic Acid Inhibits Cell Proliferation through a Suppression of c-Myc Protein in Pancreatic Ductal Adenocarcinoma Cells.Antioxidants (Basel, Switzerland) · 2021Article
- Histological and transcriptional characterization of the pancreatic acinar tissue in type 1 diabetes.BMJ open diabetes research & care · 2021Article
- Avoiding Time-Related Biases: A Feasibility Study on Antidiabetic Drugs and Pancreatic Cancer Applying the Parametric g-Formula to a Large German Healthcare Database.Clinical epidemiology · 2021Article
- Type 2 Diabetes Mellitus Intersects With Pancreatic Cancer Diagnosis and Development.Frontiers in oncology · 2021Review
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetes mellitus is a well-known risk factor for pancreatic cancer. We focused on hyperglycemia, a main feature of diabetes mellitus, and uncovered its effect on precancerous pancreatic intraepithelial neoplasia (PanIN) progression. In vivo induction of hyperglycemia with 100 mg/kg streptozotocin in KrasLSL G12D Pdx1Cre (KP) mice promoted the PanIN formation and progression. Preconditioning with a high- or low-glucose medium for 28 days showed that a high-glucose environment increased cell viability and sphere formation in PANC-1, a Kras-mutant human pancreatic ductal adenocarcinoma cell line, and mPKC1, a Kras-mutant murine pancreatic cancer cell line. In contrast, no changes were observed in BxPC3, a Kras-wild-type human pancreatic cancer cell line. Orthotopic injection of mPKC1 into the pancreatic tails of BL6/J mice showed that cells maintained in high-glucose medium grew into larger tumors than did those maintained in low-glucose medium. Hyperglycemia strengthened the STAT3 phosphorylation, which was accompanied by elevated MYC expression in Kras-mutant cells. Immunohistochemistry showed stronger phosphorylated STAT3 (pSTAT3) and MYC staining in PanINs from diabetic KP mice than in those from euglycemic counterparts. STAT3 inhibition with 1 μM STAT3 inhibitor STATTIC in Kras-mutant pancreatic cell lines blocked the cell viability- and sphere formation-enhancing effects of the hyperglycemic environment and reversed the elevated pSTAT3 and MYC expression. MYC knockdown did not affect cell viability but did reduce sphere formation. No decrease in pSTAT3 expression was observed upon siMYC treatment. In conclusion, hyperglycemia, on a Kras-mutant background, aggravates the PanIN progression, which is accompanied by elevated pSTAT3 and MYC expression.
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