ENKUR acts as a tumor suppressor in lung adenocarcinoma cells through PI3K/Akt and MAPK/ERK signaling pathways

Lung adenocarcinoma (LAD) is the most common type of lung cancer with a high possibility of tumor relapse and metastasis. ENKUR (Enkurin) was originally identified as a potential regulator or effector of TRPC channels that directly binds to several TRPC proteins and the p85 subunit of PI3K. However, the role of ENKUR in cancer development has remained unclear. In this study we analyzed the expression profile of ENKUR mRNA in clinical LAD samples and examined ENKUR mRNA expression and ENKUR protein level in LAD cells. Significant down-regulated ENKUR expression was observed in clinical tumor tissues of LAD as well as in human LAD cells. To evaluate the effects of aberrant ENKUR expression on cellular biology of LAD cells in vitro and tumor growth in vivo, ENKUR-overexpressed and -silenced LAD cell lines were constructed using lentiviral vectors. Our results showed that overexpression of ENKUR in LAD cells inhibited cell proliferation, migration and invasion, while silencing of ENKUR led to the opposite effects. Silencing of ENKUR in LAD cells also promoted tumorigenesis in nude mice model and caused epithelial to mesenchymal transition (EMT). Furthermore, using western blot and co-immunoprecipitation analyses, we demonstrated that ENKUR interacts with PI3K directly and is possibly involved in the PI3K/Akt and MAPK/ERK signaling pathways.