Journal
CANCER BIOMARKERS
Volume 13, Issue 5, Pages 329-336Publisher
IOS PRESS
DOI: 10.3233/CBM-130362
Keywords
Integrin beta 1; epidermal-mesenchymal transition; EGFR TKI; resistance; non-small cell lung cancer
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Funding
- Natural Science Foundation of China [81172101, 81201706]
- Foundation of Shanghai Municipal Bureau [20124Y 123]
- Program for Young Excellent Talents in Tongji University [1511219011]
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We have previously shown that integrin beta 1 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 beta 1 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 beta 1 reverses EMT, meanwhile overexpression and activation of integrin beta 1 aggravates EMT. Lastly, we further identified that integrin beta 1 enhanced EMT via FAK-AKT signaling pathway. These findings highlight a novel relation of integrin beta 1 and EMT in EGFR TKI resistant NSCLC.
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