LHX6 Affects Erlotinib Resistance and Migration of EGFR-Mutant Non-Small-Cell Lung Cancer HCC827 Cells Through Suppressing Wnt/β-Catenin Signaling.

Background miR-214 has been reported to contribute to erlotinib resistance in non-small-cell lung cancer (NSCLC) through targeting LHX6; however, the molecular mechanisms underlying the involvement of LHX6 in mediating the resistance to EGFR-TKIs in erlotinib-resistant NSCLC HCC827 (HCC827/ER) cells remain unknown. This study aimed to investigate the mechanisms responsible for the contribution of LHX6 to EGFR-TKIs resistance in HCC827/ER cells. Materials and Methods HCC827/ER cells were generated by erlotinib treatment at a dose-escalation scheme. LHX6 knockout or overexpression was modeled in HCC827 and HCC827/ER cells, and then erlotinib IC50 values were measured. The cell migration ability was evaluated using a transwell migration assay, and the TCF/LEF luciferase activity was assessed with a TCF/LEF reporter luciferase assay. LHX6, β-catenin and Cyclin D1 expression was quantified using qPCR and Western blotting assays. In addition, the LHX6 expression was detected in lung cancer and peri-cancer specimens using immunohistochemical staining, and the associations of LHX expression with the clinicopathological characteristics of lung cancer were evaluated. Results Lower LHX6 expression was detected in HCC827/ER cells than in HCC827 cells (P 0.05). Conclusion LHX6 down-regulation may induce EGFR-TKIs resistance and increase the migration ability of HCC827/ER cells via activation of the Wnt/β-catenin pathway.