TY - JOUR AB - Patients with non‑small cell lung cancer (NSCLC) treated with EGFR‑tyrosine kinase inhibitors (TKIs) ultimately develop drug resistance and metastasis. Therefore, there is a need to identify the underlying mechanisms of resistance to EGFR‑TKIs. In the present study, colony formation and MTT assays were performed to investigate cell viability following treatment with icotinib. Gene Expression Omnibus datasets were used to identify genes associated with resistance. Wound healing and Transwell assays were used to detect cell migration and invasion with icotinib treatment and integrin α5‑knockdown. The expression levels of integrin α5 and downstream genes were detected using western blotting. Stable icotinib‑resistant (IcoR) cell lines (827/IcoR and PC9/IcoR) were established that showed enhanced malignant properties compared with parental cells (HCC827 and PC9). Furthermore, the resistant cell lines were resistant to icotinib in terms of proliferation, migration and invasion. The enrichment of function and signaling pathways analysis showed that integrin α5‑upregulation was associated with the development of icotinib resistance. The knockdown of integrin α5 attenuated the migration and invasion capability of the resistant cells. Moreover, a combination of icotinib and integrin α5 siRNA significantly inhibited migration and partly restored icotinib sensitivity in IcoR cells. The expression levels of phosphorylated (p)‑focal adhesion kinase (FAK), p‑STAT3 and p‑AKT decreased after knockdown of integrin α5, suggesting that FAK/STAT3/AKT signaling had a notable effect on the resistant cells. The present study revealed that the integrin α5/FAK/STAT3/AKT signaling pathway promoted icotinib resistance and malignancy in IcoR NSCLC cells. This signaling pathway may provide promising targets against acquired resistance to EGFR‑TKI in patients with NSCLC. AD - Department of Respiratory and Infectious Disease of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China Department of Medical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China AU - Yang,Yang AU - Wang,Yizhe AU - Che,Xiaofang AU - Hou,Kezuo AU - Wu,Jie AU - Zheng,Chunlei AU - Cheng,Yang AU - Liu,Yunpeng AU - Hu,Xuejun AU - Zhang,Jingdong DA - 2021/07/01 DO - 10.3892/ol.2021.12817 IS - 1 JO - Oncol Lett KW - icotinib resistance integrin α5 migration invasion metastasis PY - 2021 SN - 1792-1074 1792-1082 SP - 556 ST - Integrin α5 promotes migration and invasion through the FAK/STAT3/AKT signaling pathway in icotinib‑resistant non‑small cell lung cancer cells T2 - Oncology Letters TI - Integrin α5 promotes migration and invasion through the FAK/STAT3/AKT signaling pathway in icotinib‑resistant non‑small cell lung cancer cells UR - https://doi.org/10.3892/ol.2021.12817 VL - 22 ER -