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

Journal of Experimental & Clinical Cancer Research

Biao He⁴  David M Jablons⁴  Changli Wang¹  Xishan Hao¹  Hua Zhang¹  Huaiyin Shi²  Qingfeng Zheng⁵  Minli Mo³  Etienne Giroux-Leprieur⁴  Thomas M Luh⁴  Joy Q Jin⁴  Hsin-Hui K Tseng⁴  Yi Zhang⁷  Juanjuan Che⁶  Hui Li⁴  Dongsheng Yue⁴ 

[1] Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center of Cancer, Tianjin 300060, China;Department of pathology, Chinese PLA General Hospital, Fu-xing Road #28, Beijing 100853, China;School of Life Sciences, Tsinghua University, Beijing 10084, China;Department of Surgery, Thoracic Oncology Program, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA;Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing 100142, China;Department of Oncology, Beijing Friendship Hospital of Capital Medical University, Beijing 100050, China;Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China

关键词: Lung squamous cell carcinoma;    EMT;    Gli;    Sonic Hedgehog;   

Others  :  804005
DOI  :  10.1186/1756-9966-33-34

 received in 2014-02-21, accepted in 2014-04-15,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Yue et al.; licensee BioMed Central Ltd.

【 图 表 】

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