Sphingosine kinase 1 is a potential therapeutic target for nasopharyngeal carcinoma.

Wenhua Li,Jian Li,Yunchao Wang,Zhihua Ruan,Ni Li,Keqian Zhang,Zhiqiang Tian,Bing Ni,Huaizhi Wang

doi:10.18632/oncotarget.13014

Abstract

Sphingosine kinase 1 (SPHK1) has been shown to be involved in the progression of various types of human cancers. We previously demonstrated that SPHK1 is overexpressed and associated with clinical stage, locoregional recurrence, distant metastasis and poor prognosis in nasopharyngeal carcinoma (NPC). However, the biological roles involving SPHK1 and its potential usefulness as a therapeutic target in NPC remain unknown. In this study, Blocking SPHK1 using siRNA or FTY720 (a SPHK1 inhibitor) significantly reduced proliferation and migration and increased cell cycle arrest and apoptosis in NPC cells. FTY720 also decreased SPHK1 activity, and overexpressing SPHK1 abrogated the FTY720-induced effects on cell viability. In addition, FTY720 sensitized NPC cells to radiotherapy by inhibiting SPHK1 activity in vitro and in vivo. Furthermore, high SPHK1 expression was associated with increased Ki-67 and p-Akt and decreased caspase-3 expression in human NPC specimens. These data suggest that SPHK1 might be a potential therapeutic target for NPC.

Highlights

Nasopharyngeal carcinoma (NPC) is a head and neck epithelial malignant tumor that occurs frequently in Southeast Asia, especially in Southern China [1, 2]
High Sphingosine kinase 1 (SPHK1) expression was associated with increased Ki-67 and p-Akt and decreased caspase-3 expression in human nasopharyngeal carcinoma (NPC) specimens
We found that SPHK1 protein levels are elevated in NPC and that high expression levels of SPHK1 are associated with clinical stage, locoregional recurrence, distant metastasis and poor prognosis in NPC [19]

Summary

Introduction

Nasopharyngeal carcinoma (NPC) is a head and neck epithelial malignant tumor that occurs frequently in Southeast Asia, especially in Southern China [1, 2]. Sphingolipids are membrane lipids that are ubiquitously expressed in eukaryotic cells [5] Bioactive sphingolipids, such as ceramide (Cer), sphingosine (Sph), and sphingosine 1-phophate (S1P), act as bioeffector molecules. These factors are involved in the regulation of various aspects of cancer pathogenesis, and they affect how therapies work by influencing cell proliferation, apoptosis, migration, senescence or responses to stressful conditions [6, 7]. The balance between proapoptotic ceramide and pro-survival S1P has been viewed as a sphingolipid rheostat that determines cell fate [10]. This balance is tightly regulated, mainly by sphingosine kinase 1 (SPHK1), which catalyzes the phosphorylation of sphingosine to produce pro-survival S1P [11]

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