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Hung JY, Yen MC, Jian SF, et al. Secreted protein acidic and rich in cysteine (SPARC) induces cell migration and epithelial mesenchymal transition through WNK1/snail in non-small cell lung cancer. Oncotarget. 2017;8(38):63691-63702doi: 10.18632/oncotarget.19475.
Hung, J. Y., Yen, M. C., Jian, S. F., Wu, C. Y., Chang, W. A., Liu, K. T., Hsu, Y. L., Chong, I. W., & Kuo, P. L. (2017). Secreted protein acidic and rich in cysteine (SPARC) induces cell migration and epithelial mesenchymal transition through WNK1/snail in non-small cell lung cancer. Oncotarget, 8(38), 63691-63702. https://doi.org/10.18632/oncotarget.19475
Hung, Jen-Yu, et al. "Secreted protein acidic and rich in cysteine (SPARC) induces cell migration and epithelial mesenchymal transition through WNK1/snail in non-small cell lung cancer." Oncotarget vol. 8,38 (2017): 63691-63702. doi: https://doi.org/10.18632/oncotarget.19475
Hung JY, Yen MC, Jian SF, Wu CY, Chang WA, Liu KT, Hsu YL, Chong IW, Kuo PL. Secreted protein acidic and rich in cysteine (SPARC) induces cell migration and epithelial mesenchymal transition through WNK1/snail in non-small cell lung cancer. Oncotarget. 2017 Jul 22;8(38):63691-63702. doi: 10.18632/oncotarget.19475. eCollection 2017 Sep 08. PMID: 28969021; PMCID: PMC5609953.
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Oncotarget. 2017 Jul 22;8(38):63691-63702. doi: 10.18632/oncotarget.19475. eCollection 2017 Sep 08.

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

Oncotarget

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

Affiliations

  1. School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  2. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
  3. Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
  4. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  5. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  6. Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  7. Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan.

PMID: 28969021 PMCID: PMC5609953 DOI: 10.18632/oncotarget.19475

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.

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

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

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