ArticleBMC cancer2010
Activating transcription factor-3 (ATF3) functions as a tumor suppressor in colon cancer and is up-regulated upon heat-shock protein 90 (Hsp90) inhibition.
Article in BMC cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 89 citations in OpenAlex.
- Cancer Stemness and Dedifferentiation in Anaplastic Thyroid Carcinoma: Insights into a Multigenic, Microenvironmental Network and the Role of CD44.Biomedicines · 2026Review
- HDAC7-Induced Epigenetic Repression Modulates ATF3 Functional Plasticity in Colorectal Cancer Pathogenesis.International journal of biological sciences · 2026Article
- CCDC86-BHLHE40-ATF3 axis promotes aerobic glycolysis and tumor development in glioma.Genes & diseases · 2025Article
- Targeting polyunsaturated fatty acids desaturase FADS1 inhibits renal cancer growth via ATF3-mediated ER stress response.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Understanding the intersection between placental development and cancer: Lessons from the tumor suppressor BAP1.Communications biology · 2024Review
- Activating transcription factor 3 mediates apoptosis and cell cycle arrest in TP53-mutated anaplastic thyroid cancer cells.Thyroid research · 2024Article
- Targeting Fatty Acid Desaturase I Inhibits Renal Cancer Growth Via ATF3-mediated ER Stress Response.bioRxiv : the preprint server for biology · 2024Article
- Drug-resilient Cancer Cell Phenotype Is Acquired via Polyploidization Associated with Early Stress Response Coupled to HIF2α Transcriptional Regulation.Cancer research communications · 2024Article
- Integrative transcriptomic profiling uncovers immune and functional responses to bisphenol a across multiple tissues in male mice.Animal cells and systems · 2024Article
- Ferroptosis regulates key signaling pathways in gastrointestinal tumors: Underlying mechanisms and therapeutic strategies.World journal of gastroenterology · 2023Review
- Activating transcription factor 3 inhibits NF‑κB p65 signaling pathway and mediates apoptosis and cell cycle arrest in cervical cancer cells.Infectious agents and cancer · 2022Article
- ATF3 in atherosclerosis: a controversial transcription factor.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Repurposing econazole as a pharmacological autophagy inhibitor to treat pancreatic ductal adenocarcinoma.Acta pharmaceutica Sinica. B · 2022Article
- Targeting Post-Translational Regulation of p53 in Colorectal Cancer by Exploiting Vulnerabilities in the p53-MDM2 Axis.Cancers · 2022Review
- Induction of heparanase 2 (Hpa2) expression by stress is mediated by ATF3.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- LINC00238 inhibits hepatic carcinoma progression by activating TMEM106C‑mediated apoptosis pathway.Molecular medicine reports · 2021Observational
- ATF3 promotes the serine synthesis pathway and tumor growth under dietary serine restriction.Cell reports · 2021Article
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- Inhibitory role of ATF3 in gastric cancer progression through regulating cell EMT and stemness.Cancer cell international · 2021Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundActivating transcription factor-3 (ATF3) is involved in the complex process of cellular stress response. However, its exact role in cancer is discussed controversially because both tumor suppressive and oncogenic effects have been described. Here we followed-up on our previous observation that inhibition of Hsp90 may increase ATF3 expression and sought to determine the role of ATF3 in colon cancer.
methodsRegulation of ATF3 was determined in cancer cells using signaling inhibitors and a heat-shock protein-90 (Hsp90) antagonist. Human HCT116 cancer cells were stably transfected with an ATF3-shRNA or a luciferase-shRNA expression plasmid and alterations in cell motility were assessed in migration assays. The impact of ATF3 down-regulation on cancer growth and metastasis were investigated in a subcutaneous tumor model, a model of hepatic tumor growth and in a model of peritoneal carcinomatosis. Human colon cancer tissues were analyzed for ATF3 expression.
resultsThe results show that therapeutic Hsp90 inhibition substantially up-regulates the expression of ATF3 in various cancer cells, including colon, gastric and pancreatic cancer. This effect was evident both in vitro and in vivo. RNAi mediated knock-down of ATF3 in HCT116 colon cancer cells significantly increased cancer cell migration in vitro. Moreover, in xenogenic mouse models, ATF3 knock-down promoted subcutaneous tumor growth and hepatic metastasis, as well as peritoneal carcinomatosis. Importantly, ATF3 expression was lower in human colon cancer specimens, as compared to corresponding normal surrounding tissues, suggesting that ATF3 may represent a down-regulated tumor suppressor in colon cancer.
conclusionIn conclusion, ATF3 down-regulation in colon cancer promotes tumor growth and metastasis. Considering that blocking Hsp90 induces ATF3 expression, Hsp90 inhibition may represent a valid strategy to treat metastatic colon cancer by up-regulating this anti-metastatic transcription factor.
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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.