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

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 this study, we found that FA treatment dose-dependently inhibited the proliferation, invasion and migration of NPC cells, via folate receptor alpha (FRα). We further found that FA, bounding 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 of TSLC1 expression In addition, knockdown of TSLC1 abolished the FA-mediated inhibition of cell proliferation, invasion and migration, and suppressed the FA-mediated increase of E-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.