SCUBE2 inhibits the proliferation, migration and invasion of human non-small cell lung cancer cells through regulation of the sonic hedgehog signaling pathway

Signal peptide-CUB-EGF domain-containing protein 2 (SCUBE2) belongs to a secreted and membrane-associated multi-domain SCUBE protein family. Recently, it was found to play an important role in tumor development. However, the role of SCUBE2 in non-small cell lung cancer (NSCLC) has never been revealed. Here, we explored the roles and mechanism of SCUBE2 in the progression of NSCLC. Our result showed that SCUBE2 was expressed in low levels in NSCLC cell lines. In addition, overexpression of SCUBE2 significantly inhibited the proliferation, migration and invasion of NSCLC cells. Further mechanistic analysis showed that SCUBE2 overexpression efficiently inhibited the protein expression of Shh, Smo, and Gli1 in NSCLC cells. Moreover, experiments with recombinant sonic hedgehog protein rh-Shh dramatically dampened the decrease in cell proliferation, invasion, and migration triggered by SCUBE2. Taken together, these results suggest that overexpression of SCUBE2 inhibits NSCLC cell proliferation and invasion through suppressing the Sonic hedgehog signaling pathway. Thus, SCUBE2 may be a potential therapeutic target for NSCLC.