RASSF10 suppresses lung cancer proliferation and invasion by decreasing the level of phosphorylated LRP6.

ABSTRACT

Ras-association domain family (RASSF) proteins exert distinct cellular functions. The expression of RASSF10 in non-small cell lung cancer and its underlying mechanism have not been reported. Herein, we explored the roles of RASSF10 in lung cancer cells and potential molecular mechanisms. We found low RASSF10 expression in lung cancer specimens, which was associated with low differentiation, advanced pTNM stage, positive lymph node metastasis, and poor prognosis in patients. Furthermore, RASSF10 overexpression inhibited the proliferation and invasion of lung cancer cells, which was the result of Wnt signaling suppression. However, we found that RASSF10 had no influence on Hippo signaling, while RASSF10 bound to LRP6 via the coiled-coil domains and reduced p-LRP6 level, eventually prohibiting ß-catenin nuclear translocation. However, deleting the coiled-coil domains ablated this function. These findings expound the interaction between RASSF10 and LRP6 and uncover a potential link between N-terminal RASSFs and the Wnt pathway.