Research Papers:

Gli promotes epithelial-mesenchymal transition in human lung adenocarcinomas

Hui Li, Dongsheng Yue, Joy Q. Jin, Gavitt A. Woodard, Bhairavi Tolani, Thomas M. Luh, Etienne Giroux-Leprieur, Minli Mo, Zhao Chen, Juanjuan Che, Zhenfa Zhang, Yong Zhou, Lei Wang, Xishan Hao, David Jablons, Changli Wang and Biao He _

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Oncotarget. 2016; 7:80415-80425. https://doi.org/10.18632/oncotarget.11246

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Hui Li1,*, Dongsheng Yue1,2,*, Joy Q. Jin1, Gavitt A. Woodard1, Bhairavi Tolani1, Thomas M. Luh1, Etienne Giroux-Leprieur1, Minli Mo3, Zhao Chen3, Juanjuan Che4, Zhenfa Zhang2, Yong Zhou1, Lei Wang1,5, Xishan Hao2, David Jablons1, Changli Wang2, Biao He1

1Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA

2Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China

3Beijing ACCB Biotech Ltd., Beijing 100084, China

4Department of Oncology, Beijing Friendship Hospital of Capital Medical University, Beijing 100050, China

5Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China

*These authors have contributed equally to this work

Correspondence to:

Biao He, email: [email protected]

Changli Wang, email: [email protected]

Keywords: sonic hedgehog, gli, epithelial-mesenchymal transition, lung cancer, adenocarcinoma

Received: May 09, 2016     Accepted: July 28, 2016     Published: August 12, 2016


Adenocarcinoma is the most common type of lung cancer. Epithelial-mesenchymal transition (EMT) is required for tumor invasion/metastasis and the components that control this process are potential therapeutic targets. This study we examined the role of Gli in lung adenocarcinoma and whether its activation regulates metastasis through EMT in lung adenocarcinoma. We found that tumors with high Gli expression had significantly lower E-Cadherin expression in two independent cohorts of patients with lung adenocarcinoma that we studied. In vitro up-regulation of SHh resulted in increased cell migration while small molecule inhibitors of Smo or Gli significantly reduced cell mobility both in a wound healing assay and in a 3D cell invasion assay. Inhibition of Gli in vivo decreased tumor growth and induced an increase in E-Cadherin expression. Our results indicate that Gli may be critical for lung adenocarcinoma metastasis and that a novel Gli inhibitor shows promise as a therapeutic agent by preventing cell migration and invasion in vitro and significantly reducing tumor growth and increasing E-Cadherin expression in vivo.

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