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Oncotarget. 2016 Dec 6;7(49):80415-80425. doi: 10.18632/oncotarget.11246.

Gli promotes epithelial-mesenchymal transition in human lung adenocarcinomas.

Author information

1
Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
2
Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
3
Beijing ACCB Biotech Ltd., Beijing 100084, China.
4
Department of Oncology, Beijing Friendship Hospital of Capital Medical University, Beijing 100050, China.
5
Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.

Abstract

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.

KEYWORDS:

adenocarcinoma; epithelial-mesenchymal transition; gli; lung cancer; sonic hedgehog

PMID:
27533453
PMCID:
PMC5348330
DOI:
10.18632/oncotarget.11246
[Indexed for MEDLINE]
Free PMC Article

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