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Increased SPK1 expression promotes cell growth by activating the ERK1/2 signaling in non-small-cell lung cancer

Yang, Yanga,*; Zhao, Jiea,*; Hao, Dongb; Wang, Xiaozhib; Wang, Taob; Li, Hongbob; Lv, Bingjieb

doi: 10.1097/CAD.0000000000000733

Lung cancer remains the leading cause of cancer-associated mortality in China and the world. Increasing numbers of studies have reported that sphingosine kinase 1 (SPK1) is frequently highly expressed in tumors of various origins, including lung cancer, and its high expression contributes toward tumor progression. However, the clinical significance of SPK1 and its role in the growth and metastasis of non-small-cell lung cancer (NSCLC) remain unclear. In the present study, we found that SPK1 expression was expressed highly in NSCLC tissues and cell lines. Knockdown of SPK1 suppressed cell growth, proliferation, migration, and invasion and increased apoptosis. Moreover, knocking down SPK1 expression inhibited the growth of tumors in nude mice. Mechanistically, silencing the expression of SPK1 inhibited the expression of p-extracellular signal-regulated kinase (ERK). Moreover, the ERK-specific inhibitor U0126 suppressed the expression of the epithelial–mesenchymal transition of lung cancer cells. Together, our findings indicated that SPK1 enhanced tumor growth in lung cancer and induced metastasis by activating the ERK1/2 signaling pathway, indicating its potential application in NSCLC diagnosis and therapy.

Departments of aGeriatrics

bRespirator Medicine and Intensive Care Unit, Affiliated Hospital of Binzhou Medical University, Binzhou, China

*Yang Yang and Jie Zhao contributed equally to the writing of this article.

Correspondence to Bingjie Lv, MSc, Department of Respirator Medicine and Intensive Care Unit, Affiliated Hospital of Binzhou Medical University, Binzhou, 256603 Shandong Province, China Tel: +86 543 325 8595; fax: +86 543 325 8595; e-mail:

Received July 4, 2018

Accepted November 22, 2018

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