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

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

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

66 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 language	English
Pages (from-to)	1341-1352
Number of pages	12
Journal	Cell Death and Differentiation
Volume	22
Issue number	8
DOIs	https://doi.org/10.1038/cdd.2014.228
Publication status	Published - 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.

Publisher Copyright:
© 2015 Macmillan Publishers Limited.

All Science Journal Classification (ASJC) codes

Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/cdd.2014.228

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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

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title = "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 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.",

author = "Moon, {Y. W.} and G. Rao and Kim, {J. J.} and Shim, {H. S.} and Park, {K. S.} and An, {S. S.} and B. Kim and Steeg, {P. S.} and S. Sarfaraz and {Changwoo Lee}, L. and Donna Voeller and Choi, {E. Y.} and Ji Luo and D. Palmieri and Chung, {H. C.} and Kim, {J. H.} and Y. Wang and G. Giaccone",

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. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",

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doi = "10.1038/cdd.2014.228",

language = "English",

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T1 - LAMC2 enhances the metastatic potential of lung adenocarcinoma

AU - Moon, Y. W.

AU - Rao, G.

AU - Kim, J. J.

AU - Shim, H. S.

AU - Park, K. S.

AU - An, S. S.

AU - Kim, B.

AU - Steeg, P. S.

AU - Sarfaraz, S.

AU - Changwoo Lee, L.

AU - Voeller, Donna

AU - Choi, E. Y.

AU - Luo, Ji

AU - Palmieri, D.

AU - Chung, H. C.

AU - Kim, J. H.

AU - Wang, Y.

AU - Giaccone, G.

N1 - 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. Publisher Copyright: © 2015 Macmillan Publishers Limited.

PY - 2015/8/7

Y1 - 2015/8/7

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.

AB - 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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LAMC2 enhances the metastatic potential of lung adenocarcinoma

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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