Integrin beta 1 enhances the epithelial-mesenchymal transition in association with gefitinib resistance of non-small cell lung cancer

Article type: Research Article

Authors: Ju, Lixia^a | Zhou, Caicun^{b; *}

Affiliations: [a] Department of Traditional Chinese Medicine, Shanghai Pulmonary Hospital, Tongji University, Medical School, Shanghai, China | [b] Department of Oncology and Cancer Institute, Shanghai Pulmonary Hospital, Tongji University, Medical School, Shanghai, China

Correspondence: [*] Corresponding author: Dr. Caicun Zhou, Department of Oncology, Shanghai Pulmonary Hospital, Tongji University, Medical School, 507 Zhengmin Road, Shanghai, 200433, China. Tel.: +86 21 65115006 ext. 3051; E-mail: caicunzhou@yahoo.com.cn.

Abstract: We have previously shown that integrin β1 associates with gefitinib resistance. As epithelial-mesenchymal transition (EMT) also induces gefitinib resistance in vitro, we wished to determine the relation of them in gefitinib resistance. In this study, we show that integrin β1 induced epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in xenograft tumors and gefitinib-resistant NSCLC tumors acquired EMT phenotype. Furthermore, inhibition of integrin β1 reverses EMT, meanwhile overexpression and activation of integrin β1 aggravates EMT. Lastly, we further identified that integrin β1 enhanced EMT via FAK-AKT signaling pathway. These findings highlight a novel relation of integrin β1 and EMT in EGFR TKI resistant NSCLC.

Keywords: Integrin beta 1, epidermal-mesenchymal transition, EGFR TKI, resistance, non-small cell lung cancer

DOI: 10.3233/CBM-130362

Journal: Cancer Biomarkers, vol. 13, no. 5, pp. 329-336, 2013