Wnt7a inhibits transformed cell proliferation while promoting migration and invasion in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the most important cause of lung cancer death. Wnt7a is a known tumor suppressor gene which is often downregulated in NSCLC, and restoration of Wnt7a leads to decreased NSCLC cell proliferation. However, the biological role of Wnt7a in the migration and invasion in NSCLC remains unclear. We examined whether overexpression of Wnt7a transfected by pcDNA6-Wnt7a could induce the proliferation, migration and invasion of NSCLC H1650 and A549 cell lines. Wnt7a signaling pathway, such as canonical (β-catenin) or non-canonical (c-Jun N-terminal kinase, JNK) pathways, were also assessed. We found that re-expression of Wnt7a led to reduced cell growth in NSCLC cell lines. In spite of the antiproliferative effect, Wnt7a overexpression could affect the migration and invasion of NSCLC cells. In the Wnt7a signaling pathway, the phosphorylation of JNK (Thr-183/Tyr-185) and c-Jun (Ser-63) were increased by re-expression of Wnt7a in both H1650 and A549 cell lines. The phosphorylation of β-catenin (Thr-41/Ser-45, Ser-552, Ser-675, and Ser-45) were not altered by restoration of Wnt7a. In NSCLC cells, Wnt7a overexpression was accompanied by parallel changes in the JNK pathway but not in the β-catenin pathway. These results help to understand that Wnt7a may play a two-sided role in NSCLC, suggesting that restoration of Wnt7a expression is not always suitable as therapeutic strategy for NSCLC.