title: 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.
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Pan
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Che
authors.forename: Daming
authors.initials: D
authors.lastname: Cui
authors.forename: Chao
authors.initials: C
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D005910:Glioma / Q000473:pathology*; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D034622:RNA Interference / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D055815:Young Adult; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1