title: LAMC2 enhances the metastatic potential of lung adenocarcinoma.
abstract: Lung cancer is the number one cancer killer, and metastasis is the main cause of high mortality in lung cancer patients. However, mechanisms underlying the development of lung cancer metastasis remain unknown. Using genome-wide transcriptional analysis in an experimental metastasis model, we identified laminin γ2 (LAMC2), an epithelial basement membrane protein, to be significantly upregulated in lung adenocarcinoma metastatic cells. Elevated LAMC2 increased traction force, migration, and invasion of lung adenocarcinoma cells accompanied by the induction of epithelial-mesenchymal transition (EMT). LAMC2 knockdown decreased traction force, migration, and invasion accompanied by EMT reduction in vitro, and attenuated metastasis in mice. LAMC2 promoted migration and invasion via EMT that was integrin β1- and ZEB1-dependent. High LAMC2 was significantly correlated with the mesenchymal marker vimentin expression in lung adenocarcinomas, and with higher risk of recurrence or death in patients with lung adenocarcinoma. We suggest that LAMC2 promotes metastasis in lung adenocarcinoma via EMT and may be a potential therapeutic target.
authors.affiliation: 1] Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA [2] Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Y W
authors.initials: YW
authors.lastname: Moon
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: G
authors.initials: G
authors.lastname: Rao
authors.affiliation: Department of Bioengineering, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: H-S
authors.initials: HS
authors.lastname: Shim
authors.affiliation: 1] Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA [2] Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: K-S
authors.initials: KS
authors.lastname: Park
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: An
authors.affiliation: Pathology Branch, National Cancer Institute, National Institutes of Health, MD, USA.
authors.forename: B
authors.initials: B
authors.lastname: Kim
authors.affiliation: Women's Cancers Section, Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Steeg
authors.affiliation: Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sarfaraz
authors.affiliation: Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: L
authors.initials: L
authors.lastname: Changwoo Lee
authors.affiliation: Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Voeller
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: E Y
authors.initials: EY
authors.lastname: Choi
authors.affiliation: Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Luo
authors.affiliation: Women's Cancers Section, Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: D
authors.initials: D
authors.lastname: Palmieri
authors.affiliation: Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: H C
authors.initials: HC
authors.lastname: Chung
authors.affiliation: Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: 1] Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA [2] Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1] Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA [2] Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: G
authors.initials: G
authors.lastname: Giaccone
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051379:Mice
chemical_list: C400567:LAMC2 protein, human; C498522:Lamc2 protein, mouse; D007797:Laminin