Folic acid inhibits nasopharyngeal cancer cell proliferation and invasion via activation of FRα/ERK1/2/TSLC1 pathway.

Zhibiao Liu,Wen Pi,Xin Jin,Shouhou Liu

doi:10.1042/bsr20170772

Abstract

Folic acid (FA), which is necessary for normal cell division of mammals, has been implicated to be involved in many tumors. Dietary FA intake has been reported to be associated with a lower risk of nasopharyngeal cancer (NPC). However, the molecular mechanisms of FA in NPC cells remain unclear. In the present study, we found that FA treatment dose dependently inhibited the proliferation, invasion and migration of NPC cells, via folate receptor α (FRα). We further found that FA, bound to FRα, induced the activation of MEK/ERK1/2, and increased the expressions of TSLC1 and E-cadherin. Moreover, blocking of ERK1/2 activation attenuated FA-mediated increase in TSLC1 expression. In addition, knockdown of TSLC1 abolished the FA-mediated inhibition of cell proliferation, invasion and migration, and suppressed the FA-mediated increase oinE-cadherin expression in NPC cells. Taken together, our data suggest that FA treatment inhibits NPC cell proliferation and invasion via activation of FRα/ERK1/2/ TSLC1 signaling pathway. Therefore, FA could be explored as a therapeutic drug for the treatment of NPC, and TSLC1 may act as a tumor suppressor in NPC.

Highlights

Nasopharyngeal cancer (NPC) is the most common cancer arising from the epithelium of nasopharynx, and has a high incidence in Southern China [1]
We further examined the effect of Folic acid (FA) treatment on NPC cell invasion and migration
By real-time PCR and Western blot analysis, we found that FA treatment concentration dependently increased E-cadherin expression of HONE1 cells, at both mRNA and protein levels (Figure 2D,E)

Summary

Introduction

Nasopharyngeal cancer (NPC) is the most common cancer arising from the epithelium of nasopharynx, and has a high incidence in Southern China [1]. NPC is characterized by its highly invasive and metastatic tendencies, and the prognosis is very poor once metastasis occurs [4]. It is important and urgent to uncover the molecular mechanisms involved in the invasion and metastasis of NPC, and to find new drugs that can improve the prognosis of NPC patients. It is reported that dietary FA intake is protective for NPC in a high-risk population of Chinese adults [8]. Folate receptor α (FRα), a single chain glycosyl-phosphatidylinositol-anchored membrane protein, is the major transporter of FA and acts as an important mediator in many cancers [9]. The molecular mechanisms of FA and FRα in NPC progression remain elusive

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Results

Conclusion