Oncotarget

Research Papers:

Secreted protein acidic and rich in cysteine (SPARC) induces cell migration and epithelial mesenchymal transition through WNK1/snail in non-small cell lung cancer

Jen-Yu Hung, Meng-Chi Yen, Shu-Fang Jian, Cheng-Ying Wu, Wei-An Chang, Kuan-Ting Liu, Ya-Ling Hsu, Inn-Wen Chong _ and Po-Lin Kuo

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Oncotarget. 2017; 8:63691-63702. https://doi.org/10.18632/oncotarget.19475

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Abstract

Jen-Yu Hung1,2, Meng-Chi Yen3, Shu-Fang Jian4, Cheng-Ying Wu4, Wei-An Chang2,4, Kuan-Ting Liu1,3,4, Ya-Ling Hsu5, Inn-Wen Chong2,6 and Po-Lin Kuo4,7

1School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

3Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

4Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

5Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

6Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

7Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan

Correspondence to:

Inn-Wen Chong, email: [email protected]

Po-Lin Kuo, email: [email protected]

Keywords: SPARC, WNK1, lung cancer, EMT, migration

Received: March 24, 2017    Accepted: June 20, 2017    Published: July 22, 2017

ABSTRACT

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.


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