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 language | English (US) |
---|---|
Pages (from-to) | 2401-2408 |
Number of pages | 8 |
Journal | Anticancer research |
Volume | 33 |
Issue number | 6 |
State | Published - 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