Association of integrin beta1 and c-MET in mediating EGFR TKI gefitinib resistance in non-small cell lung cancer

Cancer Cell International

Caicun Zhou²  Lixia Ju¹ 

[1] Department of Traditional Chinese Medicine, Shanghai Pulmonary Hospital, Tongji University, Medical School, Shanghai, 200433, China;Cancer Institute, Department of Oncology, Shanghai Pulmonary Hospital, Tongji University, Medical School, 507 Zhengmin Road, Shanghai, 200433, China

关键词: Resistance;    EGFR TKI;    c-MET;    Integrin beta1;    Non-small cell lung cancer;   

Others  :  794346
DOI  :  10.1186/1475-2867-13-15

 received in 2012-11-14, accepted in 2013-01-28,  发布年份 2013

【 摘 要 】

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. In our previous study we found that integrin beta1 can induce EGFR TKIs resistance in non-small cell lung cancer (NSCLC) cells. Here we analyzed the association of integrin beta1 and c-MET that is a recognized mechanism of EGFR TKIs resistance in NSCLC to demonstrate the mechanism of integrin beta1 related EGFR TKIs resistance. We found that the ligands of integrin beta1 and c-MET could synergistically promote cell proliferation and their inhibitors could synergistically improve the sensitivity to gfitinib, increase apoptosis, and inhibit the downstream signal transduction: focal adhesion kinase (FAK) and AKT. On the other hand, ligand-dependent activation of integrin beta1 could induce EGFR TKIs resistance through activating c-MET and its downstream signals. Thus, it can be concluded that there is crosstalk between integrin beta1 and c-MET and integrin beta1 mediates EGFR TKI resistance associating with c-MET signaling pathway in non-small cell lung cancer.

【 授权许可】

   
2013 Ju and Zhou; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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