Cargando…
Secreted protein acidic and rich in cysteine (SPARC) induces cell migration and epithelial mesenchymal transition through WNK1/snail in non-small cell lung cancer
The extracellular matrix is a component of physiological microenvironment and a regulator of cellular processes such as migration and proliferation. Secreted Protein Acidic and Rich in Cysteine (SPARC/osteonectin) is an extracellular matrix-associated glycoprotein involved in the regulation of cell...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609953/ https://www.ncbi.nlm.nih.gov/pubmed/28969021 http://dx.doi.org/10.18632/oncotarget.19475 |
_version_ | 1783265696893894656 |
---|---|
author | Hung, Jen-Yu Yen, Meng-Chi Jian, Shu-Fang Wu, Cheng-Ying Chang, Wei-An Liu, Kuan-Ting Hsu, Ya-Ling Chong, Inn-Wen Kuo, Po-Lin |
author_facet | Hung, Jen-Yu Yen, Meng-Chi Jian, Shu-Fang Wu, Cheng-Ying Chang, Wei-An Liu, Kuan-Ting Hsu, Ya-Ling Chong, Inn-Wen Kuo, Po-Lin |
author_sort | Hung, Jen-Yu |
collection | PubMed |
description | The extracellular matrix is a component of physiological microenvironment and a regulator of cellular processes such as migration and proliferation. Secreted Protein Acidic and Rich in Cysteine (SPARC/osteonectin) is an extracellular matrix-associated glycoprotein involved in the regulation of cell proliferation and cell migration in several types of cancers. However, the role of SPARC in lung cancer is paradoxical and details of the regulatory mechanism are not well-known. In this study, we investigated novel SPARC-mediated signaling pathways. Treatment of SPARC increased cell proliferation, migration, and mesenchymal phenotype in two non-small cell lung cancer cell lines, CL1-5 and H1299. We found that these phenotypes were not regulated by focal adhesion kinase and Src kinase, but were mediated by with no lysine (K) kinase 1 (WNK1). Suppression of WNK1 expression decreased the expression of SPARC-induced N-cadherin and smooth muscle actin. Moreover, Snail, an important transcription factor for regulating epithelial–mesenchymal transition, is also involved in SPARC/WNK1 pathway. In a murine tumor model, SPARC treatment significantly induced phosphorylation of Akt and WNK1 in lung tumor nodules when compared to control mice. In conclusion, these data suggest that WNK1 is a novel molecule in SPARC-mediated mesenchymal signaling pathway in non-small cell lung cancer. |
format | Online Article Text |
id | pubmed-5609953 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56099532017-09-29 Secreted protein acidic and rich in cysteine (SPARC) induces cell migration and epithelial mesenchymal transition through WNK1/snail in non-small cell lung cancer Hung, Jen-Yu Yen, Meng-Chi Jian, Shu-Fang Wu, Cheng-Ying Chang, Wei-An Liu, Kuan-Ting Hsu, Ya-Ling Chong, Inn-Wen Kuo, Po-Lin Oncotarget Research Paper The extracellular matrix is a component of physiological microenvironment and a regulator of cellular processes such as migration and proliferation. Secreted Protein Acidic and Rich in Cysteine (SPARC/osteonectin) is an extracellular matrix-associated glycoprotein involved in the regulation of cell proliferation and cell migration in several types of cancers. However, the role of SPARC in lung cancer is paradoxical and details of the regulatory mechanism are not well-known. In this study, we investigated novel SPARC-mediated signaling pathways. Treatment of SPARC increased cell proliferation, migration, and mesenchymal phenotype in two non-small cell lung cancer cell lines, CL1-5 and H1299. We found that these phenotypes were not regulated by focal adhesion kinase and Src kinase, but were mediated by with no lysine (K) kinase 1 (WNK1). Suppression of WNK1 expression decreased the expression of SPARC-induced N-cadherin and smooth muscle actin. Moreover, Snail, an important transcription factor for regulating epithelial–mesenchymal transition, is also involved in SPARC/WNK1 pathway. In a murine tumor model, SPARC treatment significantly induced phosphorylation of Akt and WNK1 in lung tumor nodules when compared to control mice. In conclusion, these data suggest that WNK1 is a novel molecule in SPARC-mediated mesenchymal signaling pathway in non-small cell lung cancer. Impact Journals LLC 2017-07-22 /pmc/articles/PMC5609953/ /pubmed/28969021 http://dx.doi.org/10.18632/oncotarget.19475 Text en Copyright: © 2017 Hung et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Hung, Jen-Yu Yen, Meng-Chi Jian, Shu-Fang Wu, Cheng-Ying Chang, Wei-An Liu, Kuan-Ting Hsu, Ya-Ling Chong, Inn-Wen Kuo, Po-Lin Secreted protein acidic and rich in cysteine (SPARC) induces cell migration and epithelial mesenchymal transition through WNK1/snail in non-small cell lung cancer |
title | Secreted protein acidic and rich in cysteine (SPARC) induces cell migration and epithelial mesenchymal transition through WNK1/snail in non-small cell lung cancer |
title_full | Secreted protein acidic and rich in cysteine (SPARC) induces cell migration and epithelial mesenchymal transition through WNK1/snail in non-small cell lung cancer |
title_fullStr | Secreted protein acidic and rich in cysteine (SPARC) induces cell migration and epithelial mesenchymal transition through WNK1/snail in non-small cell lung cancer |
title_full_unstemmed | Secreted protein acidic and rich in cysteine (SPARC) induces cell migration and epithelial mesenchymal transition through WNK1/snail in non-small cell lung cancer |
title_short | Secreted protein acidic and rich in cysteine (SPARC) induces cell migration and epithelial mesenchymal transition through WNK1/snail in non-small cell lung cancer |
title_sort | secreted protein acidic and rich in cysteine (sparc) induces cell migration and epithelial mesenchymal transition through wnk1/snail in non-small cell lung cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609953/ https://www.ncbi.nlm.nih.gov/pubmed/28969021 http://dx.doi.org/10.18632/oncotarget.19475 |
work_keys_str_mv | AT hungjenyu secretedproteinacidicandrichincysteinesparcinducescellmigrationandepithelialmesenchymaltransitionthroughwnk1snailinnonsmallcelllungcancer AT yenmengchi secretedproteinacidicandrichincysteinesparcinducescellmigrationandepithelialmesenchymaltransitionthroughwnk1snailinnonsmallcelllungcancer AT jianshufang secretedproteinacidicandrichincysteinesparcinducescellmigrationandepithelialmesenchymaltransitionthroughwnk1snailinnonsmallcelllungcancer AT wuchengying secretedproteinacidicandrichincysteinesparcinducescellmigrationandepithelialmesenchymaltransitionthroughwnk1snailinnonsmallcelllungcancer AT changweian secretedproteinacidicandrichincysteinesparcinducescellmigrationandepithelialmesenchymaltransitionthroughwnk1snailinnonsmallcelllungcancer AT liukuanting secretedproteinacidicandrichincysteinesparcinducescellmigrationandepithelialmesenchymaltransitionthroughwnk1snailinnonsmallcelllungcancer AT hsuyaling secretedproteinacidicandrichincysteinesparcinducescellmigrationandepithelialmesenchymaltransitionthroughwnk1snailinnonsmallcelllungcancer AT chonginnwen secretedproteinacidicandrichincysteinesparcinducescellmigrationandepithelialmesenchymaltransitionthroughwnk1snailinnonsmallcelllungcancer AT kuopolin secretedproteinacidicandrichincysteinesparcinducescellmigrationandepithelialmesenchymaltransitionthroughwnk1snailinnonsmallcelllungcancer |