LAMC2 enhances the metastatic potential of lung adenocarcinoma

Y W Moon; G Rao; J J Kim; H-S Shim; K-S Park; S S An; B Kim; P S Steeg; S Sarfaraz; L Changwoo Lee; Donna Voeller; E Y Choi; Ji Luo; D Palmieri; H C Chung; J-H Kim; Y Wang; G Giaccone

doi:10.1038/cdd.2014.228

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LAMC2 enhances the metastatic potential of lung adenocarcinoma

Journal article

Open access

Peer reviewed

LAMC2 enhances the metastatic potential of lung adenocarcinoma

Y W Moon, G Rao, J J Kim, H-S Shim, K-S Park, S S An, B Kim, P S Steeg, S Sarfaraz, L Changwoo Lee, …

Cell death and differentiation, Vol.22(8), pp.1341-1352

08/2015

DOI: https://doi.org/10.1038/cdd.2014.228

PMCID: PMC4495359

PMID: 25591736

Abstract

Adenocarcinoma - pathology

Adenocarcinoma of Lung

Epithelial-Mesenchymal Transition - physiology

Humans

Lung Neoplasms - metabolism

Lung Neoplasms - pathology

Epithelial-Mesenchymal Transition - genetics

Cell Movement - genetics

Cell Movement - physiology

Laminin - genetics

Adenocarcinoma - metabolism

Animals

Cell Line, Tumor

Female

Mice

Laminin - metabolism

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.

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Title: LAMC2 enhances the metastatic potential of lung adenocarcinoma
Creators: Y W Moon - 1] Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
G Rao - Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA
J J Kim - Department of Bioengineering, Johns Hopkins University, Baltimore, MD, USA
H-S Shim - Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea
K-S Park - 1] Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA
S S An - Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, USA
B Kim - Pathology Branch, National Cancer Institute, National Institutes of Health, MD, USA
P S Steeg - Women's Cancers Section, Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
S Sarfaraz - Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
L Changwoo Lee - Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Donna Voeller - Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
E Y Choi - Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, USA
Ji Luo - Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
D Palmieri - Women's Cancers Section, Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
H C Chung - Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
J-H Kim - Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
Y Wang - 1] Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA
G Giaccone - 1] Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA
Publication Details: Cell death and differentiation, Vol.22(8), pp.1341-1352
Date published: 08/2015
Grant note: HL107361 / NHLBI NIH HHS P30 CA051008 / NCI NIH HHS R43 CA141868 / NCI NIH HHS P50CA103175 / NCI NIH HHS P50 CA103175 / NCI NIH HHS U54CA141868 / NCI NIH HHS P30 CA51008 / NCI NIH HHS R01 HL107361 / NHLBI NIH HHS U54 CA143868 / NCI NIH HHS
Academic Unit: Clinical and Translational Research
Language: English
Resource Type: Journal article
Identifiers: 991031654695704646