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

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1341-1352
Number of pages12
JournalCell Death and Differentiation
Volume22
Issue number8
DOIs
Publication statusPublished - 2015 Aug 7

Bibliographical note

Funding Information:
Acknowledgements. We thank Dr. Jhingook Kim for providing the GSE8894 data, Dr. Miyazaki for pBOS-CITE-Neo-γ2 vector, Dr. Lynn Young for help with expression array data analysis, Yongzhen Qian for help with intracardiac injection, and Dr. Joon-Yong Chung for help with IHC. This study was supported by NIH intramural program and by NIH P30 CA51008 grant. SS An was funded by the NIH P50CA103175, U54CA141868 and HL107361 grants.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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