ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Amphiregulin promotes BAX inhibition and resistance to gefitinib in non-small-cell lung cancers.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- A defect of amphiregulin release predicted longer survival independently of YAP expression in patients with pleural mesothelioma in the IFCT-0701 MAPS phase 3 trial.International journal of cancer · 2022Trial
- Amphiregulin drives EGFR-dependent genome stability in colorectal cancer and represents a targetable vulnerability.Oncogene · 2026Article
- STK25 inhibits cancer-associated fibroblast activation to overcome cetuximab resistance in colorectal cancer.Clinical and translational medicine · 2026Article
- Amphiregulin in Fibrotic Diseases and Cancer.International journal of molecular sciences · 2025Review
- Pannexin1 via P2rx7/amphiregulin contributes to cardiac fibrosis post myocardial infarction.Journal of molecular histology · 2025Article
- APOBEC3 Activity Promotes the Survival and Evolution of Drug-Tolerant Persister Cells during EGFR Inhibitor Resistance in Lung Cancer.Cancer research communications · 2025Article
- Amivantamab efficacy in wild-type EGFR NSCLC tumors correlates with levels of ligand expression.NPJ precision oncology · 2024Article
- A Transcriptomic Approach to Elucidate the Mechanisms of Gefitinib-Induced Toxicity in Healthy Human Intestinal Organoids.International journal of molecular sciences · 2022Article
- miR-196a Upregulation Contributes to Gefitinib Resistance through Inhibiting GLTP Expression.International journal of molecular sciences · 2022Article
- Article
- Disease-related cellular protein networks differentially affected under different EGFR mutations in lung adenocarcinoma.Scientific reports · 2020Article
- Therapeutic Targeting of Signaling Pathways Related to Cancer Stemness.Frontiers in oncology · 2020Review
- AhR controls redox homeostasis and shapes the tumor microenvironment in BRCA1-associated breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Amphiregulin Regulates Phagocytosis-Induced Cell Death in Monocytes via EGFR and the Bcl-2 Protein Family.Mediators of inflammation · 2019Article
- Inverse Correlation of STAT3 and MEK Signaling Mediates Resistance to RAS Pathway Inhibition in Pancreatic Cancer.Cancer research · 2018Article
- Molecular Markers of Anticancer Drug Resistance in Head and Neck Squamous Cell Carcinoma: A Literature Review.Cancers · 2018Review
- The Role of Hippo Pathway in Cancer Stem Cell Biology.Molecules and cells · 2018Review
- Incense burning smoke sensitizes lung cancer cells to EGFR TKI by inducing AREG expression.American journal of cancer research · 2018Article
- EGF receptor signaling, phosphorylation, ubiquitylation and endocytosis in tumors in vivo.eLife · 2017Article
- A nonimmune function of T cells in promoting lung tumor progression.The Journal of experimental medicine · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Molecular resistance mechanisms affecting the efficiency of receptor tyrosine kinase inhibitors such as gefitinib in non-small-cell lung cancer (NSCLC) cells are not fully understood. Amphiregulin (Areg) overexpression has been proposed to predict NSCLC resistance to gefitinib and we have established that Areg-overexpressing H358 NSCLC cells resist apoptosis. Here, we demonstrate that Areg prevents gefitinib-induced apoptosis in NSCLC cells. We show that H358 cells are resistant to gefitinib in contrast to H322 cells, which do not overexpress Areg. Inhibition of Areg expression by small-interfering RNAs (siRNAs) restores gefitinib sensitivity in H358 cells, whereas addition of recombinant Areg confers resistance in H322 cells. Areg knockdown overcomes resistance to gefitinib and induced apoptosis in NSCLC H358 cells in vitro and in vivo. Under gefitinib treatment, Areg decreases the expression of the proapoptotic protein BAX, inhibits its conformational change and its mitochondrial translocation. Thus, in the presence of Areg, gefitinib-mediated apoptosis is reduced because BAX is sequestered in the cytoplasm. This suggests that treatments using epidermal growth factor receptor (EGFR) inhibitors may be poorly efficient in patients with elevated levels of Areg. These findings indicate the need for inhibition of Areg to enhance the efficiency of the EGFR inhibitors in patients suffering NSCLC.
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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.