Metastasis is the leading cause of cancer mortality and is a major hurdle for lung cancer treatment. Invadopodia, which are cancer-specific protrusive structures, play a crucial role in the metastatic cascade through degradation of the basement membrane and surrounding stroma, but the exact mechanism of regulation is not yet fully understood. In this study, we show that cortactin (CTTN), an important component of invadopodia, is upregulated in lung cancer tissues and is a marker of poorer prognosis in human NSCLC. Phorbol 12,13-dibutyrate and hepatocyte growth factor can induce CTTN expression and motility, as well as invadopodia formation in non-small cell lung cancer (NSCLC). MicroRNA-182 (miR-182) suppresses metastasis and invadopodia formation by targeting CTTN in NSCLC. qRT-PCR results showed that CTTN expression was inversely correlated with expression of miR-182. miR-182/CTTN suppresses invadopodia formation of lung cancer cells via suppression of the Cdc42/N-WASP pathway. Furthermore, miR-182 negatively regulates invadopodia function and suppresses extracellular matrix degradation in lung cancer cells by inhibiting CTTN. In conclusion, our results demonstrated that miR-182 targets CTTN in NSCLC and suppresses lung cancer invadopodia formation and thus suppresses lung cancer metastasis, suggesting a therapeutic application of miR-182 in NSCLC.

Citation Format: Yongwen Li, Hongbing Zhang, Hongyu Liu, Jun Chen. MiR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4420.