Dataset Information

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 ?2 (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 ?1- 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.

SUBMITTER: Moon YW

PROVIDER: S-EPMC4495359 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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LAMC2 enhances the metastatic potential of lung adenocarcinoma.

Moon Y W YW Rao G G Kim J J JJ Shim H-S HS Park K-S KS An S S SS Kim B B Steeg P S PS Sarfaraz S S Changwoo Lee L L Voeller Donna D Choi E Y EY Luo Ji J Palmieri D D Chung H C HC Kim J-H JH Wang Y Y Giaccone G G

Cell death and differentiation 20150116 8

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 invasi ...[more]

PMID: 25591736

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Project description:Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer with an abysmal prognosis rate over the last few decades. Early diagnosis and prevention could effectively combat this malignancy. Therefore, it is crucial to discover potential biomarkers to identify asymptomatic premalignant or early malignant tumors of PDAC. Gene expression analysis is a powerful technique to identify candidate biomarkers involved in disease progression. In the present study, five independent gene expression datasets, including 321 PDAC tissues and 208 adjacent non-cancerous tissue samples, were subjected to statistical and bioinformatics analysis. A total of 20 differentially expressed genes (DEGs) were identified in PDAC tissues compared to non-cancerous tissue samples. Gene ontology and pathway enrichment analysis showed that DEGs were mainly enriched in extracellular matrix (ECM), cell adhesion, ECM-receptor interaction, and focal adhesion signaling. The protein-protein interaction network was constructed, and the hub genes were evaluated. Collagen type XII alpha 1 chain (COL12A1), fibronectin 1 (FN1), integrin subunit alpha 2 (ITGA2), laminin subunit beta 3 (LAMB3), laminin subunit gamma 2 (LAMC2), thrombospondin 2 (THBS2), and versican (VCAN) were identified as hub genes. The correlation analysis revealed that identified hub genes were significantly interconnected. Wherein COL12A1, FN1, ITGA2, LAMB3, LAMC2, and THBS2 were significantly associated with PDAC pathological stages. The Kaplan-Meier survival plots revealed that ITGA2, LAMB3, and LAMC2 expression were inversely correlated with a prolonged patient survival period. Furthermore, the Human Protein Atlas database was used to validate the expression and cellular origins of hub genes encoded proteins. The protein expression of hub genes was higher in pancreatic cancer tissue than in normal pancreatic tissue samples, wherein ITGA2, LAMB3, and LAMC2 were exclusively expressed in pancreatic cancer cells. Pancreatic cancer cell-specific expression of these three proteins may play pleiotropic roles in cancer progression. Our results collectively suggest that ITGA2, LAMB3, and LAMC2 could provide deep insights into pancreatic carcinogenesis molecular mechanisms and provide attractive therapeutic targets.

Dataset Information

LAMC2 enhances the metastatic potential of lung adenocarcinoma.

Publications

LAMC2 enhances the metastatic potential of lung adenocarcinoma.

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