ArticleGenes2021
Krüppel-Like Factor 4 and Its Activator APTO-253 Induce NOXA-Mediated, p53-Independent Apoptosis in Triple-Negative Breast Cancer Cells.
Article in Genes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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
21 citing papers in PubMed, 24 citations in OpenAlex.
- Regulatory roles and translational potential of the Kruppel-like factor family in liver disease.iLIVER · 2026Review
- Multi-Protein Profiling Reveals High Nuclear KFL-4 Expression as a Predictor of Poor Overall Survival in Breast Cancer: A Retrospective Cohort Study.International journal of molecular sciences · 2026Article
- Lycium barbarum polysaccharide inhibits Hcy-induced vascular smooth muscle cells migration and invasion via upregulation of KLF4.Scientific reports · 2026Article
- Krüppel-Like Factor 4, a Hub Gate for Cell Crosstalk in Tumor Microenvironment.Cancer medicine · 2026Review
- Optimized Monothiol Thioredoxin Derivative (ORP100S) Protects In Vitro and In Vivo from Radiation and Chemotoxicity Without Promoting Tumor Proliferation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- ACTL6A depletion induces KLF4-mediated anti-tumorigenic effects in colorectal cancer.Cell death & disease · 2025Article
- Narciclasine enhances cisplatin-induced apoptotic cell death by inducing unfolded protein response-mediated regulation of NOXA and MCL1.Cellular & molecular biology letters · 2025Article
- Artesunate Inhibits Neointimal Hyperplasia by Promoting IRF4 Associated Macrophage Polarization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Stemness of Cancer: A Study of Triple-negative Breast Cancer From a Neuroscience Perspective.Stem cell reviews and reports · 2025Review
- The KLF4/Galectin-3 cascade is a key determinant of tubular cell death and acute kidney injury.International journal of biological sciences · 2025Article
- Quercetin Attenuates KLF4-Mediated Phenotypic Switch of VSMCs to Macrophage-like Cells in Atherosclerosis: A Critical Role for the JAK2/STAT3 Pathway.International journal of molecular sciences · 2024Article
- Article
- Cuproptosis-Related Genes MTF1 and LIPT1 as Novel Prognostic Biomarker in Acute Myeloid Leukemia.Biochemical genetics · 2024Article
- FAM3A reshapes VSMC fate specification in abdominal aortic aneurysm by regulating KLF4 ubiquitination.Nature communications · 2023Article
- Synthetic Reader-Actuators Targeted to Polycomb-Silenced Genes Block Triple-Negative Breast Cancer Proliferation and Invasion.GEN biotechnology · 2023Article
- Development and validation of an endoplasmic reticulum stress-related molecular prognostic model for breast cancer.Frontiers in oncology · 2023Article
- Krüppel-like factors in tumors: Key regulators and therapeutic avenues.Frontiers in oncology · 2023Review
- KLF4 is a therapeutically tractable brake on fibroblast activation that promotes resolution of pulmonary fibrosis.JCI insight · 2022Article
- Article
- Identification of biomarkers in nonalcoholic fatty liver disease: A machine learning method and experimental study.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inducing apoptosis is an effective treatment for cancer. Conventional cytotoxic anticancer agents induce apoptosis primarily through activation of tumor suppressor p53 by causing DNA damage and the resulting regulation of B-cell leukemia/lymphoma-2 (BCL-2) family proteins. Therefore, the effects of these agents are limited in cancers where p53 loss-of-function mutations are common, such as triple-negative breast cancer (TNBC). Here, we demonstrate that ultraviolet (UV) light-induced p53-independent transcriptional activation of NOXA, a proapoptotic factor in the BCL-2 family, results in apoptosis induction. This UV light-induced NOXA expression was triggered by extracellular signal-regulated kinase (ERK) activity. Moreover, we identified the specific UV light-inducible DNA element of the NOXA promoter and found that this sequence is responsible for transcription factor Krüppel-like factor 4 (KLF4)-mediated induction. In p53-mutated TNBC cells, inhibition of KLF4 by RNA interference reduced NOXA expression. Furthermore, treatment of TNBC cells with a KLF4-inducing small compound, APTO-253, resulted in the induction of NOXA expression and NOXA-mediated apoptosis. Therefore, our results help to clarify the molecular mechanism of DNA damage-induced apoptosis and provide support for a possible treatment method for p53-mutated cancers.
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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 Socratic graph.