179P - Integrin beta1 mediates EGFR TKI resistance through c-MET signaling pathway in non-small cell lung cancer

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Thoracic Malignancies
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Lixia Ju
Authors L. Ju1, C. Zhou2
  • 1Traditional Chinese Medicine, Shanghai Pulmonary Hospital, Tongji University, 200433 - shanghai/CN
  • 2Oncology, Shanghai Pulmonary Hospital, 200433 - Shanghai/CN



Although some patients are initially sensitive to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), resistance invariably develops. Therefore, it's very important to study the molecular mechanism of this resistance. For the first time, we found that integrin �1 associates with EGFR TKIs resistance. We also investigated the crosstalk between integrin �1 and c-MET that is a recognized mechanism of EGFR TKIs resistance in non-small cell lung cancer (NSCLC) to explore the mechanism.

Materials and methods

We study the the crosstalk between integrin �1 and c-MET using MTT, Western blot, TUNEL, xenograft model and immunohistochemical.


We found that integrin �1 and c-MET co-expressed in PC9 and PC9/AB2 cell lines and the ligands of integrin �1 and c-MET could synergistically promote cell proliferation and their inhibitors could synergistically improve the sensitivity to gefitinib, increase apoptosis, and inhibit the phosphoralation of their downstream signal transduction: FAK and AKT. Ligand-dependent activation of integrin �1 could induce EGFR TKIs resistance and decreased gefitinib-induced apoptosis through activating c-MET and its downstream signals: FAK and AKT. On the other hand, in integrin �1 overexpressed xenograft tumor models, gefitinib couldn't inhibit the tumors growth effectively and reduce phosphorylation of AKT, FAK and c-MET effectively.


Herein, it can be concluded that there is crosstalk between integrin �1 and c-MET and integrin�1 mediates EGFR TKI resistance through c-MET signaling pathway in non-small cell lung cancer.


All authors have declared no conflicts of interest.