Integrin beta 1 enhances the epithelial-mesenchymal transition in association with gefitinib resistance of non-small cell lung cancer.
We have previously shown that integrinβ1 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 integrinβ1 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 integrinβ1 reverses EMT, meanwhile overexpression and activation of integrinβ1 aggravates EMT. Lastly, we further identified that integrinβ1 enhanced EMT via FAK-AKT signaling pathway. These findings highlight a novel relation of integrinβ1 and EMT in EGFR TKI resistant NSCLC.
Department of Traditional Chinese Medicine, Shanghai Pulmonary Hospital, Tongji University, Medical School, Shanghai, China.
Lixia
L
Ju
Department of Oncology and Cancer Institute, Shanghai Pulmonary Hospital, Tongji University, Medical School, Shanghai, China.
Caicun
C
Zhou
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000502:physiology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D011799:Quinazolines / Q000494:pharmacology*; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D019012:Integrin beta1; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
EGFR TKI; Integrin beta 1; epidermal-mesenchymal transition; non-small cell lung cancer; resistance