title: Sensitivity to epidermal growth factor receptor tyrosine kinase inhibitor requires E-cadherin in esophageal cancer and malignant pleural mesothelioma.
abstract: OBJECTIVE
  Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has limited anticancer efficacy in EGFR-positive esophageal cancer (EsC) and malignant mesothelioma (MPM). The underlying molecular mechanism of resistance to EGFR-TKI in these types of cancer remains unclear.
  
  
  METHODS
  We tested sensitivity to EGFR-TKI, expression/activity of common signal transduction pathways and epithelial to mesenchymal transition (EMT) gene signatures in 14 EsC and MPM cultured cell lines in vitro.
  
  
  RESULTS
  More than 50% EGFR-positive EsC and MPM cells were resistant to EGFR-TKI, and susceptibility to EGFR-TKI growth-inhibitory effect correlated positively with expression of E-cadherin (epithelial gene marker) and negatively with mesenchymal gene markers. Acquired resistance to EGFR-TKI in intrinsically sensitive cancer cells coincided with spontaneous loss of E-cadherin, while ectopic expression of E-cadherin sensitized resistant cells to EGFR-TKI.
  
  
  CONCLUSIONS
  E-Cadherin expression appears to be not only a strong biomarker but also a functional requirement and potential therapeutic target for sensitivity to EGFR-TKI.
authors.affiliation: Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Hong-Wu
authors.initials: HW
authors.lastname: Xin
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Yang
authors.forename: Dao M
authors.initials: DM
authors.lastname: Nguyen
mesh_terms: D014408:Biomarkers, Tumor; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008654:Mesothelioma / Q000188:drug therapy* / Q000378:metabolism; D000086002:Mesothelioma, Malignant; D011799:Quinazolines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D004791:Enzyme Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; C088860:4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline
keywords: E-Cadherin; epidermal growth factor receptor; epithelial to mesenchymal transition (EMT); esophageal cancer; malignant pleural mesothelioma; tyrosine kinase inhibitor