ArticlePloS one2012
Activating transcription factor 4 confers a multidrug resistance phenotype to gastric cancer cells through transactivation of SIRT1 expression.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed.
- GCN2 in Cancer: Molecular Mechanisms to Therapeutic Potential.Current cancer drug targets · 2026Review
- ER stress and/or ER-phagy in drug resistance? Three coincidences are proof.Cell communication and signaling : CCS · 2025Review
- The role of SIRT1 in the development of gastrointestinal tumors.Frontiers in cell and developmental biology · 2025Review
- Article
- Article
- ATGL promotes colorectal cancer growth by regulating autophagy process and SIRT1 expression.Medical oncology (Northwood, London, England) · 2023Article
- Sirtuins (SIRTs) As a Novel Target in Gastric Cancer.International journal of molecular sciences · 2022Review
- Review
- Metal-dependent programmed cell death-related lncRNA prognostic signatures and natural drug sensitivity prediction for gastric cancer.Frontiers in pharmacology · 2022Article
- High ATF4 Expression Is Associated With Poor Prognosis, Amino Acid Metabolism, and Autophagy in Gastric Cancer.Frontiers in oncology · 2021Article
- Biochemical mechanism and biological effects of the inhibition of silent information regulator 1 (SIRT1) by EX-527 (SEN0014196 or selisistat).Journal of enzyme inhibition and medicinal chemistry · 2020Article
- Altered Expression of CD44, SIRT1, CXCR4, miR-21, miR-34a, and miR-451 Genes in MKN-45 Cell Line After Docetaxel Treatment.Journal of gastrointestinal cancer · 2020Article
- LASP1 induces colorectal cancer proliferation and invasiveness through Hippo signaling and Nanog mediated EMT.American journal of translational research · 2020Article
- Programming of Cell Resistance to Genotoxic and Oxidative Stress.Biomedicines · 2018Review
- PSAT1 is regulated by ATF4 and enhances cell proliferation via the GSK3β/β-catenin/cyclin D1 signaling pathway in ER-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2017Article
- Surviving Stress: Modulation of ATF4-Mediated Stress Responses in Normal and Malignant Cells.Trends in endocrinology and metabolism: TEM · 2017Review
- Meta-analysis of SIRT1 expression as a prognostic marker for overall survival in gastrointestinal cancer.Oncotarget · 2017Article
- SIRT1 protects the heart from ER stress-induced cell death through eIF2α deacetylation.Cell death and differentiation · 2017Article
- Glucose deprivation induces chemoresistance in colorectal cancer cells by increasing ATF4 expression.World journal of gastroenterology · 2016Article
- High glucose promotes gastric cancer chemoresistance in vivo and in vitro.Molecular medicine reports · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMultidrug resistance (MDR) in gastric cancer remains a major challenge to clinical treatment. Activating transcription factor 4 (ATF4) is a stress response gene involved in homeostasis and cellular protection. However, the expression and function of ATF4 in gastric cancer MDR remains unknown. In this study, we investigate whether ATF4 play a role in gastric cancer MDR and its potential mechanisms. METHODOLOGY/PRINCIPAL
findingsWe demonstrated that ATF4 overexpression confered the MDR phenotype to gastric cancer cells, while knockdown of ATF4 in the MDR variants induced re-sensitization. In this study we also showed that the NAD(+)-dependent histone deacetylase SIRT1 was required for ATF4-induced MDR effect in gastric cancer cells. We demonstrated that ATF4 facilitated MDR in gastric cancer cells through direct binding to the SIRT1 promoter, resulting in SIRT1 up-regulation. Significantly, inhibition of SIRT1 by small interfering RNA (siRNA) or a specific inhibitor (EX-527) reintroduced therapeutic sensitivity. Also, an increased Bcl-2/Bax ratio and MDR1 expression level were found in ATF4-overexpressing cells. CONCLUSIONS/SIGNIFICANCE: We showed that ATF4 had a key role in the regulation of MDR in gastric cancer cells in response to chemotherapy and these findings suggest that targeting ATF4 could relieve therapeutic resistance in gastric cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.