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

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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

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Moon, Y. W., Rao, G., Kim, J. J., Shim, H. S., Park, K. S., An, S. S., Kim, B., Steeg, P. S., Sarfaraz, S., Changwoo Lee, L., Voeller, D., Choi, E. Y., Luo, J., Palmieri, D., Chung, H. C., Kim, J. H., Wang, Y., & Giaccone, G. (2015). LAMC2 enhances the metastatic potential of lung adenocarcinoma. Cell Death and Differentiation, 22(8), 1341-1352. https://doi.org/10.1038/cdd.2014.228