ArticleThe Journal of clinical investigation2012
Targeting the FOXO1/KLF6 axis regulates EGFR signaling and treatment response.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 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.
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Who cites it
53 citing papers in PubMed, 86 citations in OpenAlex.
- Review
- Sushi domain-containing protein 4 binds to epithelial growth factor receptor and initiates autophagy in an EGFR phosphorylation independent manner.Journal of experimental & clinical cancer research : CR · 2022Article
- Immune checkpoint inhibitors combined with tyrosine kinase inhibitors is the treatment option of previously treated advanced non-small cell lung cancer harboring EGFR or ALK genetic aberration.Translational lung cancer research · 2022Article
- Trifluoperazine and Its Analog Suppressed the Tumorigenicity of Non-Small Cell Lung Cancer Cell; Applicability of Antipsychotic Drugs to Lung Cancer Treatment.Biomedicines · 2022Article
- The endoplasmic reticulum membrane protein Sec62 as potential therapeutic target inFrontiers in physiology · 2022Review
- Systems andFrontiers in pharmacology · 2022Article
- Article
- Targeting protein phosphatase PP2A for cancer therapy: development of allosteric pharmaceutical agents.Clinical science (London, England : 1979) · 2021Review
- LncRNA KASRT Serves as a Potential Treatment Target by Regulating SRSF1-Related KLF6 Alternative Splicing and the P21/CCND1 Pathway in Osteosarcoma: AnFrontiers in oncology · 2021Article
- Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma.Scientific reports · 2020Article
- Beyond bone biology: Lessons from team science.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2020Article
- FUT4siRNA augments the chemosensitivity of non-small cell lung cancer to cisplatin through activation of FOXO1-induced apoptosis.BMC cancer · 2020Article
- KLF4 defines the efficacy of the epidermal growth factor receptor inhibitor, erlotinib, in triple-negative breast cancer cells by repressing the EGFR gene.Breast cancer research : BCR · 2020Article
- KPT-9274, an Inhibitor of PAK4 and NAMPT, Leads to Downregulation of mTORC2 in Triple Negative Breast Cancer Cells.Chemical research in toxicology · 2020Article
- Monotherapy efficacy of blood-brain barrier permeable small molecule reactivators of protein phosphatase 2A in glioblastoma.Brain communications · 2020Article
- Artesunate induces mitochondria-mediated apoptosis of human retinoblastoma cells by upregulating Kruppel-like factor 6.Cell death & disease · 2019Article
- Protein phosphatase 2A controls ongoing DNA replication by binding to and regulating cell division cycle 45 (CDC45).The Journal of biological chemistry · 2019Article
- The tumor suppressor FOXO3a mediates the response to EGFR inhibition in glioblastoma cells.Cellular oncology (Dordrecht, Netherlands) · 2019Article
- Understanding the perspectives of forkhead transcription factors in delayed wound healing.Journal of cell communication and signaling · 2019Review
- CDRgator: An Integrative Navigator of Cancer Drug Resistance Gene Signatures.Molecules and cells · 2019Article
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
EGFR activation is both a key molecular driver of disease progression and the target of a broad class of molecular agents designed to treat advanced cancer. Nevertheless, resistance develops through several mechanisms, including activation of AKT signaling. Though much is known about the specific molecular lesions conferring resistance to anti-EGFR-based therapies, additional molecular characterization of the downstream mediators of EGFR signaling may lead to the development of new classes of targeted molecular therapies to treat resistant disease. We identified a transcriptional network involving the tumor suppressors Krüppel-like factor 6 (KLF6) and forkhead box O1 (FOXO1) that negatively regulates activated EGFR signaling in both cell culture and in vivo models. Furthermore, the use of the FDA-approved drug trifluoperazine hydrochloride (TFP), which has been shown to inhibit FOXO1 nuclear export, restored sensitivity to AKT-driven erlotinib resistance through modulation of the KLF6/FOXO1 signaling cascade in both cell culture and xenograft models of lung adenocarcinoma. Combined, these findings define a novel transcriptional network regulating oncogenic EGFR signaling and identify a class of FDA-approved drugs as capable of restoring chemosensitivity to anti-EGFR-based therapy for the treatment of metastatic lung adenocarcinoma.
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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.