ArticleMolecular oncology2018
p53-independent Noxa induction by cisplatin is regulated by ATF3/ATF4 in head and neck squamous cell carcinoma cells.
Article in Molecular oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 67 citations in OpenAlex.
- Integrated stress response activation in combination PG3 and cisplatin-treatedbioRxiv : the preprint server for biology · 2026Article
- The p53-Associated Regulation of ATF4 mRNA Expression Involves p21 and p130 in a Stress-Dependent Manner.Cells · 2026Article
- A unified therapeutic theory for treating cancer via master regulators of the universal apoptosis network.Cell death discovery · 2026Review
- UPR/ATF4/Noxa pathway overactivation through SERCA2 inhibition or ONC201 treatment combined with ABT-737 triggers apoptosis in chemoresistant ovarian cancer cells and patient-derived tumor organoids.Cell death & disease · 2026Article
- The Combination of a BCL-xL PROTAC and an mTOR Inhibitor Sensitizes Pancreatic Ductal Adenocarcinoma to KRASCancers · 2026Article
- The combination of BCL-xL PROTAC and mTOR inhibitor sensitizes pancreatic ductal adenocarcinoma to KRASbioRxiv : the preprint server for biology · 2026Article
- ONC201 enhances the cytotoxic effect of cisplatin through ATF3/ATF4/CHOP in head and neck squamous cell carcinoma cells.Oncogenesis · 2025Article
- Narciclasine enhances cisplatin-induced apoptotic cell death by inducing unfolded protein response-mediated regulation of NOXA and MCL1.Cellular & molecular biology letters · 2025Article
- PIM2 inhibition promotes MCL1 dependency in plasma cells involving integrated stress response-driven NOXA expression.Nature communications · 2025Article
- ATF4-mediated expression of NOXA is critical for Necroptosis driven by Glucose Deprivation.Frontiers in cell death · 2025Article
- Oncogenic Mutant p53 Sensitizes Non-Small Cell Lung Cancer Cells to Proteasome Inhibition via Oxidative Stress-Dependent Induction of Mitochondrial Apoptosis.Cancer research communications · 2024Article
- Article
- Macrophages originated IL-33/ST2 inhibits ferroptosis in endometriosis via the ATF3/SLC7A11 axis.Cell death & disease · 2023Article
- Stress and Liver Fibrogenesis: Understanding the Role and Regulation of Stress Response Pathways in Hepatic Stellate Cells.The American journal of pathology · 2023Review
- Suppression of Ah Receptor (AhR) increases the aggressiveness of TNBC cells and 11-Cl-BBQ-activated AhR inhibits their growth.Biochemical pharmacology · 2023Article
- Induction of Aryl Hydrocarbon Receptor-Mediated Cancer Cell-Selective Apoptosis in Triple-Negative Breast Cancer Cells by a High-Affinity Benzimidazoisoquinoline.ACS pharmacology & translational science · 2023Article
- Tumor-Suppressive Functions of the Aryl Hydrocarbon Receptor (AhR) and AhR as a Therapeutic Target in Cancer.Biology · 2023Review
- A Ubiquitination Cascade Regulating the Integrated Stress Response and Survival in Carcinomas.Cancer discovery · 2023Article
- Exploration of prognostic biomarkers in head and neck squamous cell carcinoma microenvironment from TCGA database.Annals of translational medicine · 2023Article
- Competing endogenous RNAs in human astrocytes: crosstalk and interacting networks in response to lipotoxicity.Frontiers in neuroscience · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The platinum-based DNA damaging agent cisplatin is used as a standard therapy for locally advanced head and neck squamous cell carcinoma (HNSCC). However, the mechanisms underpinning the cytotoxic effects of this compound are not entirely elucidated. Cisplatin produces anticancer effects primarily via activation of the DNA damage response, followed by inducing BCL-2 family dependent mitochondrial apoptosis. We have previously demonstrated that cisplatin induces the expression of proapoptotic BCL-2 family protein, Noxa, that can bind to the prosurvival BCL-2 family protein, MCL-1, to inactivate its function and induce cell death. Here, we show that the upregulation of Noxa is critical for cisplatin-induced apoptosis in p53-null HNSCC cells. This induction is regulated at the transcriptional level. With a series of Noxa promoter-luciferase reporter assays, we find that the CRE (cAMP response element) in the promoter is critical for the Noxa induction by cisplatin treatment. Among the CREB/ATF transcription factors, ATF3 and ATF4 are induced by cisplatin, and downregulation of ATF3 or ATF4 reduced cisplatin-induced Noxa. ATF3 and ATF4 bind to and cooperatively activate the Noxa promoter. Furthermore, ERK1 is involved in cisplatin-induced ATF4 and Noxa induction. In conclusion, ATF3 and ATF4 are important regulators that induce Noxa by cisplatin treatment in a p53-independent manner.
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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.