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Sonic Hedgehog/GLI1 signaling pathway inhibition restricts cell migration and invasion in human gliomas

Abstract Recent studies have shown that aberrant activation of Sonic Hedgehog (SHH)/GLI1 signaling pathway is involved in many kinds of human malignancies. Both in vitro and in vivo experiments demonstrate that inhibiting the pathway results in tumor regression for a fraction of gliomas which harbor an active pathway. However, little is known about the linkage between the SHH/GLI1 signaling pathway and cell migration and invasion in gliomas. In this study, we showed that GLI1 expression closely correlates with pathological grades of human gliomas by immunohistochemistry analysis of 110 cases of surgically-resected glioma tissues. Moreover, we used cyclopamine and RNA interference technique to block the SHH/GLI1 signaling to investigate the in vitro changes of glioma cells. The result showed that suppression of the pathway markedly inhibited glioma cell migration and invasion. The following quantitative RT-PCR analysis showed that decreased expressions of Snail, MMP9, and increased E-cadherin expression coincided with GLI1 knockout. Collectively, our results raise the possibility that SHH/GLI1 is a potentially anti-invasive target for therapeutic intervention in human gliomas.