ArticleInternational journal of molecular sciences2020
APE1 Promotes Pancreatic Cancer Proliferation through GFRα1/Src/ERK Axis-Cascade Signaling in Response to GDNF.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 36 citations in OpenAlex.
- Multi-omics and network pharmacology reveal the mechanisms of Scutellaria barbata D.Don and Scleromitrion diffusum (Willd.) R.J.Wang against pancreatic cancer.Scientific reports · 2026Article
- Isorhamnetin Downregulates MMP2 and MMP9 to Inhibit Development of Rheumatoid Arthritis through SRC/ERK/CREB Pathway.Chinese journal of integrative medicine · 2024Article
- New Ref-1/APE1 targeted inhibitors demonstrating improved potency for clinical applications in multiple cancer types.Pharmacological research · 2024Article
- Hallmarks of perineural invasion in pancreatic ductal adenocarcinoma: new biological dimensions.Frontiers in oncology · 2024Review
- Elevated APE1 Dysregulates Homologous Recombination and Cell Cycle Driving Genomic Evolution, Tumorigenesis, and Chemoresistance in Esophageal Adenocarcinoma.Gastroenterology · 2023Article
- Tumor-associated macrophage-derived GDNF promotes gastric cancer liver metastasis via a GFRA1-modulated autophagy flux.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- GDNF-RET signaling and EGR1 form a positive feedback loop that promotes tamoxifen resistance via cyclin D1.BMC cancer · 2023Article
- APE1 redox function is required for activation of Yes-associated protein 1 under reflux conditions in Barrett's-associated esophageal adenocarcinomas.Journal of experimental & clinical cancer research : CR · 2022Article
- Downregulation of miR-211-5p Promotes Carboplatin Resistance in Human Retinoblastoma Y79 Cells by Affecting the GDNF-LIF Interaction.Frontiers in oncology · 2022Article
- Small-molecule inhibition of APE1 induces apoptosis, pyroptosis, and necroptosis in non-small cell lung cancer.Cell death & disease · 2021Article
- Aberrantly expressed GFRα-1/RET in patients with lacrimal adenoid cystic carcinoma is associated with high recurrence risk: a retrospective study of 51 LACC cases.Cancer biology & medicine · 2021Article
- Simultaneous Treatment with Soluble Forms of GAS1 and PTEN Reduces Invasiveness and Induces Death of Pancreatic Cancer Cells.OncoTargets and therapy · 2020Article
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Pancreatic cancer is the worst exocrine gastrointestinal cancer leading to the highest mortality. Recent studies reported that aberrant expression of apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is involved in uncontrolled cell growth. However, the molecular mechanism of APE1 biological role remains unrevealed in pancreatic cancer progression. Here, we demonstrate that APE1 accelerates pancreatic cancer cell proliferation through glial cell line-derived neurotrophic factor (GDNF)/glial factor receptor α1 (GFRα1)/Src/ERK axis-cascade signaling. The proliferation of endogenous APE1 expressed-MIA PaCa-2, a human pancreatic carcinoma cell line, was increased by treatment with GDNF, a ligand of GFRα1. Either of downregulated APE1 or GFRα1 expression using small interference RNA (siRNA) inhibited GDNF-induced cancer cell proliferation. The MEK-1 inhibitor PD98059 decreased GDNF-induced MIA PaCa-2 cell proliferation. Src inactivation by either its siRNA or Src inhibitor decreased ERK-phosphorylation in response to GDNF in MIA PaCa-2 cells. Overexpression of GFRα1 in APE1-deficient MIA PaCa-2 cells activated the phosphorylation of Src and ERK. The expression of both APE1 and GFRα1 was gradually increased as progressing pancreatic cancer grades. Our results highlight a critical role for APE1 in GDNF-induced pancreatic cancer cell proliferation through APE1/GFRα1/Src/ERK axis-cascade signaling and provide evidence for future potential therapeutic drug targets for the treatment of pancreatic cancer.
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