NEDD9 promotes lung cancer metastasis through epithelial- mesenchymal transition

Metastasis is the major cause for high mortality of lung cancer with the underlying mechanisms poorly understood. The scaffolding protein neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) has been identified as a pro-metastasis gene in several types of cancers including melanoma and breast cancer. However, the exact role and related mechanism of NEDD9 in regulating lung cancer metastasis still remain largely unknown. Here, we demonstrate that NEDD9 knockdown significantly inhibits migration, invasion and metastasis of lung cancer cells in vitro and in vivo. The pro-metastasis role of Nedd9 in lung cancer is further supported by studies in mice models of spontaneous cancer metastasis. Moreover, we find that NEDD9 promotes lung cancer cell migration and invasion through the induction of epithelial-mesenchymal transition (EMT) potentially via focal adhesion kinase activation. More importantly, NEDD9 expression inversely correlates with E-cadherin expression in human lung cancer specimens, consistent with the findings from in vitro studies. Taken together, this study highlights that NEDD9 is an important mediator promotes lung cancer metastasis via EMT. What's new? The scaffolding protein NEDD9 regulates signaling molecules involved in cell invasion and metastasis, activities that are promoted in melanoma and breast cancer by upregulation of the NEDD9 gene. The present study examined the role of NEDD9 in lung cancer metastasis. In vitro and in vivo experiments demonstrated that knockdown of NEDD9 inhibits lung cancer cell migration, invasion, and metastasis, while mechanistic exploration revealed that NEDD9 promotes those activities via induction of epithelial-mesenchymal transition (EMT). Expression of NEDD9 was found to be inversely correlated with E-cadherin expression in human lung cancer specimens.