ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Targeting the oncogenic MUC1-C protein inhibits mutant EGFR-mediated signaling and survival in non-small cell lung cancer cells.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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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
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Serum Krebs von den Lungen-6 before treatment predicts the prognosis of lung cancer in Asian populations: a systematic review and meta-analysis.Frontiers in immunology · 2025Pooled it
- A randomized, open-label, two-cycle, two-crossover phase I clinical trial comparing the bioequivalence and safety of afatinib and GiotrifJournal of cancer research and clinical oncology · 2023Trial
- M1C IS NECESSARY FOR DARAXONRASIB RESISTANCE OF NSCLC KRAS(G12C) MUTANT CELLS.bioRxiv : the preprint server for biology · 2026Article
- A MUC1-ALIX complex regulates extracellular vesicle cargo loading with activated SRC to enhance pancreatic cancer progression.Cancer letters · 2026Article
- Evolution of the MUC1 gene in eutherian mammals as an adaptation responsible for the increasing incidence of cancer in humans.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- P-cadherin Overexpression Induces Partial Epithelial-to-Mesenchymal Transition and Confers Chemoresistance in Dysplastic Oral Epithelial Cells.Journal of Cancer · 2026Article
- Role of Novel Bispecific Antibodies and Immunotherapy in Non-Small Cell Lung Cancer With Common Epidermal Growth Factor Receptor Mutations.JCO precision oncology · 2025Article
- The network map of mucin 1 mediated signaling in cancer progression and immune modulation.Discover oncology · 2025Article
- A quantitative spatial cell-cell colocalizations framework enabling comparisons between in vitro assembloids and pathological specimens.Nature communications · 2025Article
- Unlocking the potential of bispecific ADCs for targeted cancer therapy.Frontiers of medicine · 2024Review
- MUC1-C Is a Common Driver of Acquired Osimertinib Resistance in NSCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2024Article
- MUC1-C is a target of salinomycin in inducing ferroptosis of cancer stem cells.Cell death discovery · 2024Article
- Phenotyping EMT and MET cellular states in lung cancer patient liquid biopsies at a personalized level using mass cytometry.Scientific reports · 2023Article
- The multifaceted role of MUC1 in tumor therapy resistance.Clinical and experimental medicine · 2023Review
- An intrinsic purine metabolite AICAR blocks lung tumour growth by targeting oncoprotein mucin 1.British journal of cancer · 2023Article
- MUC1-C is necessary for SHP2 activation and BRAF inhibitor resistance in BRAF(V600E) mutant colorectal cancer.Cancer letters · 2023Article
- Cell adhesion molecules and immunotherapy in advanced non-small cell lung cancer: Current process and potential application.Frontiers in oncology · 2023Review
- Nuclear epidermal growth factor receptor as a therapeutic target.Exploration of targeted anti-tumor therapy · 2023Review
- Emergence ofCancers · 2022Review
- Addiction of Cancer Stem Cells to MUC1-C in Triple-Negative Breast Cancer Progression.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposeNon-small cell lung cancers (NSCLC) that express EGF receptor with activating mutations frequently develop resistance to EGFR kinase inhibitors. The mucin 1 (MUC1) heterodimeric protein is aberrantly overexpressed in NSCLC cells and confers a poor prognosis; however, the functional involvement of MUC1 in mutant EGFR signaling is not known. EXPERIMENTAL
designTargeting the oncogenic MUC1 C-terminal subunit (MUC1-C) in NSCLC cells harboring mutant EGFR was studied for effects on signaling, growth, clonogenic survival, and tumorigenicity.
resultsStable silencing of MUC1-C in H1975/EGFR(L858R/T790M) cells resulted in downregulation of AKT signaling and inhibition of growth, colony formation, and tumorigenicity. Similar findings were obtained when MUC1-C was silenced in gefitinib-resistant PC9GR cells expressing EGFR(delE746_A750/T790M). The results further show that expression of a MUC1-C(CQC → AQA) mutant, which blocks MUC1-C homodimerization, suppresses EGFR(T790M), AKT and MEK → ERK activation, colony formation, and tumorigenicity. In concert with these results, treatment of H1975 and PC9GR cells with GO-203, a cell-penetrating peptide that blocks MUC1-C homodimerization, resulted in inhibition of EGFR, AKT, and MEK → ERK signaling and in loss of survival. Combination studies of GO-203 and afatinib, an irreversible inhibitor of EGFR, further demonstrate that these agents are synergistic in inhibiting growth of NSCLC cells harboring the activating EGFR(T790M) or EGFR(delE746-A750) mutants.
conclusionsThese findings indicate that targeting MUC1-C inhibits mutant EGFR signaling and survival, and thus represents a potential approach alone and in combination for the treatment of NSCLCs resistant to EGFR kinase inhibitors.
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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.