LAMC2 enhances the metastatic potential of lung adenocarcinoma

Y. W. Moon, G. Rao, J. J. Kim, H. S. Shim, K. S. Park, Steven 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 journalArticle

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 (US)
Pages (from-to)1341-1352
Number of pages12
JournalCell Death and Differentiation
Volume22
Issue number8
DOIs
StatePublished - Aug 7 2015

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Epithelial-Mesenchymal Transition
Neoplasm Metastasis
Lung Neoplasms
Traction
Laminin
Vimentin
Basement Membrane
Integrins
Membrane Proteins
Theoretical Models
Adenocarcinoma of lung
Genome
Recurrence
Mortality
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Moon, Y. W., Rao, G., Kim, J. J., Shim, H. S., Park, K. S., An, S., ... 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

LAMC2 enhances the metastatic potential of lung adenocarcinoma. / Moon, Y. W.; Rao, G.; Kim, J. J.; Shim, H. S.; Park, K. S.; An, Steven; Kim, B.; Steeg, P. S.; Sarfaraz, S.; Changwoo Lee, L.; Voeller, Donna; Choi, E. Y.; Luo, Ji; Palmieri, D.; Chung, H. C.; Kim, J. H.; Wang, Y.; Giaccone, G.

In: Cell Death and Differentiation, Vol. 22, No. 8, 07.08.2015, p. 1341-1352.

Research output: Contribution to journalArticle

Moon, YW, Rao, G, Kim, JJ, Shim, HS, Park, KS, An, S, Kim, B, Steeg, PS, Sarfaraz, S, Changwoo Lee, L, Voeller, D, Choi, EY, Luo, J, Palmieri, D, Chung, HC, Kim, JH, Wang, Y & Giaccone, G 2015, 'LAMC2 enhances the metastatic potential of lung adenocarcinoma', Cell Death and Differentiation, vol. 22, no. 8, pp. 1341-1352. https://doi.org/10.1038/cdd.2014.228
Moon, Y. W. ; Rao, G. ; Kim, J. J. ; Shim, H. S. ; Park, K. S. ; An, Steven ; Kim, B. ; Steeg, P. S. ; Sarfaraz, S. ; Changwoo Lee, L. ; Voeller, Donna ; Choi, E. Y. ; Luo, Ji ; Palmieri, D. ; Chung, H. C. ; Kim, J. H. ; Wang, Y. ; Giaccone, G. / LAMC2 enhances the metastatic potential of lung adenocarcinoma. In: Cell Death and Differentiation. 2015 ; Vol. 22, No. 8. pp. 1341-1352.
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AU - Choi, E. Y.

AU - Luo, Ji

AU - Palmieri, D.

AU - Chung, H. C.

AU - Kim, J. H.

AU - Wang, Y.

AU - Giaccone, G.

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N2 - 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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