Secreted protein acidic and rich in cysteine (SPARC) induces cell migration and epithelial mesenchymal transition through WNK1/snail in non-small cell lung cancer
Metrics: PDF 2029 views | HTML 3951 views | ?
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
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
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.