title: Gli promotes epithelial-mesenchymal transition in human lung adenocarcinomas.
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.
authors.affiliation: Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.|Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Yue
authors.affiliation: Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
authors.forename: Joy Q
authors.initials: JQ
authors.lastname: Jin
authors.affiliation: Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
authors.forename: Gavitt A
authors.initials: GA
authors.lastname: Woodard
authors.affiliation: Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
authors.forename: Bhairavi
authors.initials: B
authors.lastname: Tolani
authors.affiliation: Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Luh
authors.affiliation: Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
authors.forename: Etienne
authors.initials: E
authors.lastname: Giroux-Leprieur
authors.affiliation: Beijing ACCB Biotech Ltd., Beijing 100084, China.
authors.forename: Minli
authors.initials: M
authors.lastname: Mo
authors.affiliation: Beijing ACCB Biotech Ltd., Beijing 100084, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Oncology, Beijing Friendship Hospital of Capital Medical University, Beijing 100050, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Che
authors.affiliation: Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: Zhenfa
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.|Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: Xishan
authors.initials: X
authors.lastname: Hao
authors.affiliation: Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
authors.forename: David
authors.initials: D
authors.lastname: Jablons
authors.affiliation: Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: Changli
authors.initials: C
authors.lastname: Wang
authors.affiliation: Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
authors.forename: Biao
authors.initials: B
authors.lastname: He
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D000077192:Adenocarcinoma of Lung; D000818:Animals; D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000494:pharmacology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D000072086:Smoothened Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays; D000071676:Zinc Finger Protein GLI1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; C513384:CDH1 protein, human; D015820:Cadherins; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C509239:SHH protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor; D000071676:Zinc Finger Protein GLI1
keywords: adenocarcinoma; epithelial-mesenchymal transition; gli; lung cancer; sonic hedgehog