ArticleOncotarget2016
APE1-mediated DNA damage repair provides survival advantage for esophageal adenocarcinoma cells in response to acidic bile salts.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Acidic bile salts induce APE1-dependent PRDX2 activation to drive oxaliplatin resistance via ferroptosis inhibition.Redox biology · 2026Article
- APE1/Ref-1: multifunctional biology, selective inhibition, and the path to clinical translation.Expert opinion on therapeutic targets · 2026Review
- Targeting APE1-Redox Function Reverses SOX9-mediated Chemoresistance in Esophageal Adenocarcinoma.Gastroenterology · 2026Article
- Laparoscopic One Anastomosis Gastric Bypass as a Revisional Procedure After Failed Vertical Banded Gastroplasty: Our Center Experience.Journal of obesity · 2025Article
- Targeting APE1: Advancements in the Diagnosis and Treatment of Tumors.Protein and peptide letters · 2025Review
- Role of APE1/Ref-1 in hydrogen peroxide-induced apoptosis in human renal HK-2 cells.Kidney research and clinical practice · 2024Article
- Article
- Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons.Cells · 2023Review
- Article
- Protein adduction causes non-mutational inhibition of p53 tumor suppressor.Cell reports · 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
- The Oxidative Damage and Inflammation Mechanisms in GERD-Induced Barrett's Esophagus.Frontiers in cell and developmental biology · 2022Review
- The antioxidant response in Barrett's tumorigenesis: A double-edged sword.Redox biology · 2021Review
- Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy.Molecular cancer · 2021Review
- AnFrontiers in microbiology · 2021Article
- APE1 Upregulates MMP-14 via Redox-Sensitive ARF6-Mediated Recycling to Promote Cell Invasion of Esophageal Adenocarcinoma.Cancer research · 2019Article
- Obesity and cancer: A mechanistic overview of metabolic changes in obesity that impact genetic instability.Molecular carcinogenesis · 2019Review
- NRF2 antioxidant response protects against acidic bile salts-induced oxidative stress and DNA damage in esophageal cells.Cancer letters · 2019Article
- From genetics to signaling pathways: molecular pathogenesis of esophageal adenocarcinoma.Biochimica et biophysica acta. Reviews on cancer · 2019Review
- Activation of EGFR-DNA-PKcs pathway by IGFBP2 protects esophageal adenocarcinoma cells from acidic bile salts-induced DNA damage.Journal of experimental & clinical cancer research : CR · 2019Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Chronic Gastroesophageal Reflux Disease (GERD) is the main risk factor for the development of Barrett's esophagus (BE) and its progression to esophageal adenocarcinoma (EAC). Accordingly, EAC cells are subjected to high levels of oxidative stress and subsequent DNA damage. In this study, we investigated the expression and role of Apurinic/apyrimidinic endonuclease 1 (APE1) protein in promoting cancer cell survival by counteracting the lethal effects of acidic bile salts (ABS)-induced DNA damage. Immunohistochemistry analysis of human tissue samples demonstrated overexpression of APE1 in more than half of EACs (70 of 130), as compared to normal esophagus and non-dysplastic BE samples (P < 0.01). To mimic in vivo conditions, we treated in vitro cell models with a cocktail of ABS. The knockdown of endogenous APE1 in EAC FLO-1 cells significantly increased oxidative DNA damage (P < 0.01) and DNA single- and double-strand breaks (P < 0.01), whereas overexpression of APE1 in EAC OE33 cells reversed these effects. Annexin V/PI staining indicated that the APE1 expression in OE33 cells protects against ABS-induced apoptosis. In contrast, knockdown of endogenous APE1 in FLO-1 cells increased apoptosis under the same conditions. Mechanistic investigations indicated that the pro-survival function of APE1 was associated with the regulation of stress response c-Jun N-terminal protein kinase (JNK) and p38 kinases. Pharmacological inhibition of APE1 base excision repair (BER) function decreased cell survival and enhanced activation of JNK and p38 kinases by ABS. Our findings suggest that constitutive overexpression of APE1 in EAC may be an adaptive pro-survival mechanism that protects against the genotoxic lethal effects of bile reflux episodes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.