ArticleOncotarget2015
Afatinib induces apoptosis in NSCLC without EGFR mutation through Elk-1-mediated suppression of CIP2A.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The trial behind it
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- The Emerging Role of the Cancerous Inhibitor of Protein Phosphatase 2A in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2025Review
- The Prognostic Value of CIP2A and Its Association with CD31, E-Cadherin, and pAMPK in Lung Cancer.International journal of molecular sciences · 2025Article
- Mechanistic Insights and Clinical Implications of ELK1 in Solid Tumors: A Narrative Review.Cells · 2025Review
- PUMA mediated afatinib-induced apoptosis in glioma cells.Archives of medical science : AMS · 2025Article
- From Basic Science to Clinical Practice: The Role of Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A)/p90 in Cancer.Frontiers in genetics · 2023Review
- Novel sulphonamide-bearing methoxyquinazolinone derivatives as anticancer and apoptosis inducers: synthesis, biological evaluation andJournal of enzyme inhibition and medicinal chemistry · 2022Article
- Combined treatment with inhibitors of ErbB Receptors and Hh signaling pathways is more effective than single treatment in reducing the growth of malignant mesothelioma both in vitro and in vivo.Journal of translational medicine · 2022Article
- Metformin Enhances TKI-Afatinib Cytotoxic Effect, Causing Downregulation of Glycolysis, Epithelial-Mesenchymal Transition, and EGFR-Signaling Pathway Activation in Lung Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2022Article
- CIP2A Interacts with TopBP1 and Drives Basal-Like Breast Cancer Tumorigenesis.Cancer research · 2021Article
- Afatinib induces pro-survival autophagy and increases sensitivity to apoptosis in stem-like HNSCC cells.Cell death & disease · 2021Article
- Article
- Polyphyllin I and VII potentiate the chemosensitivity of A549/DDP cells to cisplatin by enhancing apoptosis, reversing EMT and suppressing the CIP2A/AKT/mTOR signaling axis.Oncology letters · 2019Article
- Protein phosphatase 2A (PP2A): a key phosphatase in the progression of chronic obstructive pulmonary disease (COPD) to lung cancer.Respiratory research · 2019Review
- Direct activation of PP2A for the treatment of tyrosine kinase inhibitor-resistant lung adenocarcinoma.JCI insight · 2019Article
- The red wine component ellagic acid induces autophagy and exhibits anti-lung cancer activity in vitro and in vivo.Journal of cellular and molecular medicine · 2019Article
- CIP2A depletion potentiates the chemosensitivity of cisplatin by inducing increased apoptosis in bladder cancer cells.Oncology reports · 2018Article
- Targeting Polo-like kinase 1 and TRAIL enhances apoptosis in non-small cell lung cancer.Oncotarget · 2018Article
- Antibody-assisted target identification reveals afatinib, an EGFR covalent inhibitor, down-regulating ribonucleotide reductase.Oncotarget · 2018Article
- Quantitative proteomic study of mitoxantrone-resistant NCI-H460 cell-xenograft tumors.International journal of clinical and experimental pathology · 2018Article
- Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells.Toxicology and applied pharmacology · 2017Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Afatinib has anti-tumor effect in non-small cell lung carcinoma (NSCLC) with epidermal growth factor receptor (EGFR) mutation. We found afatinib can also induce apoptosis in NSCLC cells without EGFR mutation through CIP2A pathway. Four NSCLC cell lines (H358 H441 H460 and A549) were treated with afatinib to determine their sensitivity to afatinib-induced cell death and apoptosis. The effects of CIP2A on afatinib-induced apoptosis were confirmed by overexpression and knockdown of CIP2A expression in the sensitive and resistant cells, respectively. Reduction of Elk-1 binding to the CIP2A promoter and suppression of CIP2A transcription were analyzed. In vivo efficacy of afatinib against H358 and H460 xenografts tumors were also determined in nude mice. Afatinib induced significant cell death and apoptosis in H358 and H441 cells, but not in H460 or A549 cells. The apoptotic effect of afatinib in sensitive cells was associated with downregulation of CIP2A, promotion of PP2A activity and decrease in AKT phosphorylation. Afatinib suppressed CIP2A at the gene transcription level by reducing the promoter binding activity of Elk-1. Clinical samples showed that higher CIP2A expression predicted a poor prognosis and Elk-1 and CIP2A expressions were highly correlated. In conclusion, afatinib induces apoptosis in NSCLC without EGFR mutations through Elk-1/CIP2A/PP2A/AKT pathway.
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