Gli-1 expression is associated with lymph node metastasis and tumor progression in esophageal squamous cell carcinoma.
OBJECTIVE
We investigated the expression and function of the hedgehog (Hh) pathway in human esophageal squamous cell carcinoma (ESCC).


METHODS
The expression of Hh pathway molecules were detected in 34 human ESCC cell lines by RT-PCR. Subsequently, we investigated the effects of cyclopamine, a specific inhibitor of the Hh pathway, on cell proliferation, migration and invasion. Next, the effects of siRNA targeting Gli-1 were examined. Immunohistochemically, the expression of Gli-1 was studied in 104 ESCC specimens and compared with the clinicopathological characteristics of the patients.


RESULTS
Gli-1 were expressed in 31 of 34 cell lines (91%), while Sonic hedgehog (SHh), Patched (Ptch), and Smoothened (Smo) expression was noted in all 34 cell lines. Cyclopamine significantly inhibited cell proliferation and migration in ESCC cells that expressed Gli-1. siRNA targeting Gli-1 inhibited cell growth in ESCC cells. Gli-1 was expressed in 52 of 104 cancer specimens (50%). Gli-1 expression was associated with tumor depth (p < 0.001), positive lymph node metastasis (p = 0.004) and a poor prognosis (p = 0.0047).


CONCLUSIONS
Our results raise the possibility that the inhibition of the Hh pathway could be a novel target for esophageal cancer therapy.
Mori
Yukiko
Y
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Okumura
Tomoyuki
T
Tsunoda
Shigeru
S
Sakai
Yoshiharu
Y
Shimada
Yutaka
Y
D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D011379:Prognosis; D034741:RNA, Small Interfering / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D000072086:Smoothened Receptor; D013997:Time Factors; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014704:Veratrum Alkaloids / Q000494:pharmacology*; D000071676:Zinc Finger Protein GLI1
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor; D014157:Transcription Factors; D014704:Veratrum Alkaloids; D000071676:Zinc Finger Protein GLI1; C000541:cyclopamine