机构：[1]Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.[2]Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center of Cancer, Tianjin 300060, China.[3]Department of Surgery, Thoracic Oncology Program, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.[4]Department of Oncology, Beijing Friendship Hospital of Capital Medical University, Beijing 100050, China.[5]Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.胸外科首都医科大学宣武医院[6]School of Life Sciences, Tsinghua University, Beijing 10084, China.[7]Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing 100142, China.[8]Department of pathology, Chinese PLA General Hospital, Fu-xing Road #28, Beijing 100853, China.
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 beta-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.
基金：
NIH/NCI R01CA125030
the Eileen D.Ludwig Endowed for Thoracic Oncology Research
The Bonnie J.Addario Lung Cancer Foundation
the Kazan, McClain, Abrams, Fernandez,Lyons, Greenwood, Harley & Oberman Foundation
the Ziegelmam Family Foundation
the Barbara Isackson Lung Cancer Research Fund
Tianjin Municipal Science and Technology Commission(12JCYBJC17800)
the Key Program for Anti-cancer Research of Tianjin Municipal Science and Technology Commission (12ZCDZSY15400)
第一作者机构：[1]Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.[2]Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center of Cancer, Tianjin 300060, China.[3]Department of Surgery, Thoracic Oncology Program, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.[2]Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center of Cancer, Tianjin 300060, China.[3]Department of Surgery, Thoracic Oncology Program, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
推荐引用方式(GB/T 7714)：
Dongsheng Yue,Hui Li,Juanjuan Che,et al.Hedgehog/Gli promotes epithelial-mesenchymal transition in lung squamous cell carcinomas[J].JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH.2014,33(1):doi:10.1186/1756-9966-33-34.
APA：
Dongsheng Yue,Hui Li,Juanjuan Che,Yi Zhang,Hsin-Hui K Tseng...&Biao He.(2014).Hedgehog/Gli promotes epithelial-mesenchymal transition in lung squamous cell carcinomas.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,33,(1)
MLA：
Dongsheng Yue,et al."Hedgehog/Gli promotes epithelial-mesenchymal transition in lung squamous cell carcinomas".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 33..1(2014)
医学