WWOX inhibits the invasion of lung cancer cells by downregulating RUNX2.

The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor that is lost or decreased in most human tumors. The role of WWOX in human lung carcinoma invasion is still not clear. This study aimed to elucidate the potential role of WWOX in lung cancer cell invasion. WWOX mRNA levels in human lung cancers and lung cancer cell lines were assayed by quantitative real-time PCR. WWOX in lung cancer cell lines was manipulated by transfection of expression vector or small interfering RNA. Cell migration and invasion were assessed by wound healing and/or transwell migration and invasion assays. The protein levels of WWOX, E-cadherin and RUNX2 were analyzed by western blot or immunofluorescence. WWOX expression is inversely correlated to invasiveness of lung cancer. WWOX overexpression in highly invasive H1299 cells reduced cell motility and invasiveness, and inhibited the expression of RUNX2 and its target gene matrix metalloproteinase-9 (MMP-9). Silencing WWOX in less invasive NL9980 cells resulted in opposite effects. Overexpressing RUNX2 in H1299 or silencing RUNX2 in NL9980 cells reversed the effects of WWOX. These results suggested that WWOX inhibited the invasive phenotype of lung cancer through downregulating the expression of RUNX2.