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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2014

Open Access 01-12-2014 | Research

Hedgehog/Gli promotes epithelial-mesenchymal transition in lung squamous cell carcinomas

Authors: Dongsheng Yue, Hui Li, Juanjuan Che, Yi Zhang, Hsin-Hui K Tseng, Joy Q Jin, Thomas M Luh, Etienne Giroux-Leprieur, Minli Mo, Qingfeng Zheng, Huaiyin Shi, Hua Zhang, Xishan Hao, Changli Wang, David M Jablons, Biao He

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2014

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Abstract

Background

Squamous cell carcinomas (SCC) account for approximately 30% of non-small cell lung cancer. Investigation of the mechanism of invasion and metastasis of lung SCC will be of great help for the development of meaningful targeted therapeutics. This study is intended to understand whether the activation of Hedgehog (Hh) pathway is involved in lung SCC, and whether activated Hh signaling regulates metastasis through epithelial-mesenchymal transition (EMT) in lung SCC.

Methods

Two cohorts of patients with lung SCC were studied. Protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. Protein expression levels in tissue specimens were scored and correlations were analyzed. Vismodegib and a Gli inhibitor were used to inhibit Shh/Gli activity, and recombinant Shh proteins were used to stimulate the Hh pathway in lung SCC cell lines. Cell migration assay was performed in vitro.

Results

Shh/Gli pathway components were aberrantly expressed in lung SCC tissue samples. Gli1 expression was reversely associated with the expression of EMT markers E-Cadherin and β-Catenin in lung SCC specimens. Inhibition of the Shh/Gli pathway suppressed migration and up-regulated E-Cadherin expression in lung SCC cells. Stimulation of the pathway increased migration and down-regulated E-Cadherin expression in lung SCC cells.

Conclusions

Our results suggested that the Shh/Gli pathway may be critical for lung SCC recurrence, metastasis and resistance to chemotherapy. Inhibition of the Shh/Gli pathway activity/function is a potential therapeutic strategy for the treatment of lung SCC patients.
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Metadata
Title
Hedgehog/Gli promotes epithelial-mesenchymal transition in lung squamous cell carcinomas
Authors
Dongsheng Yue
Hui Li
Juanjuan Che
Yi Zhang
Hsin-Hui K Tseng
Joy Q Jin
Thomas M Luh
Etienne Giroux-Leprieur
Minli Mo
Qingfeng Zheng
Huaiyin Shi
Hua Zhang
Xishan Hao
Changli Wang
David M Jablons
Biao He
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2014
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-33-34

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