miR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin gene

Abstract

Similar results were obtained in experiments when cells were treated with HGF (32.6% versus 21.8%, P = 0.021 for A549; 36.8% versus 25.4%, P = 0.031 for H1299, respectively). [...]silencing expression of cortactin could result in reduction of invadopodia, which induced by PDBu or HGF (Fig. 5d and e). [...]the formation of invadopodia in NSCLC cells was suppressed. miR-182 negatively regulates invadopodia function and ECM degradation in lung cancer cells by inhibiting cortactin Invadopodia are involved in ECM proteolysis, allowing tumor cells to infiltrate the stroma and vasculature. [...]many key invadopodia proteins are also cortactin-binding partners, including N-WASP, WIP, dynamin, ASAP1/AMAP1, and Src kinase [40], suggesting that cortactin also acts as a scaffolding function in invadopodia. Functionally, decreased expression of cortactin was shown to decrease cell motility in a variety of assays, including transwell migration, wound closure, and cell motility. [...]our results indicated that cortactin expression was upregulated when lung cancer cells were treated with PDBu or HGF, as well as invadopodia formation in non-small cell lung cancer cells, which indicated an important role of cortactin in invadopodia formation.