Sensitivity to epidermal growth factor receptor tyrosine kinase inhibitor requires e-cadherin in esophageal cancer and malignant pleural mesothelioma

Hong Wu Xin, Jian Hui Yang, Dao M. Nguyen

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Background/Aim: 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 EGFRTKI in these types of cancer remains unclear. Materials and 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 than50% 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)2401-2408
Number of pages8
JournalAnticancer research
Volume33
Issue number6
StatePublished - Jun 1 2013

Keywords

  • E-Cadherin
  • Epidermal growth factor receptor
  • Epithelial to mesenchymal transition (EMT)
  • Esophageal cancer
  • Malignant pleural mesothelioma
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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