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

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.

Tripartite Motif Containing 11 Interacts with DUSP6 to Promote the Growth of Human Osteosarcoma Cells through Regulating ERK1/2 Pathway

“…Growing evidence has demonstrated that the activation of the ERK1/2 pathway accelerated the proliferation of tumor cells, including oral cancer [23], nasopharyngeal cancer [24], and hepatoma cells [25]. In this analysis, our findings revealed that overexpression of TRIM11 promoted the activation of the ERK1/2 signaling pathway in OS cells.…”

Effects of folic acid withdrawal on transcriptomic profiles in murine triple-negative breast cancer cell lines

“…In another study, folate deprivation enhanced invasiveness of colon cancer cells through the activation of sonic hedgehog and NF-κB signaling [48]. Inhibitory effects of folic acid on metastasis and proliferation have been also linked to the activation of the folate receptor-ERK1/2-TSLC1 signaling pathway [49]. Contrary to these studies, we have previously reported that folate deprivation inhibits migration and invasion of cultured cancer cells and decreases tumor growth and metastasis in a mouse model [28,42,50].…”

Functionalized Folic Acid-Conjugated Amphiphilic Alternating Copolymer Actively Targets 3D Multicellular Tumour Spheroids and Delivers the Hydrophobic Drug to the Inner Core

“…The same observation was obtained previously when empty FA-DABA-SMA was applied to the PANC-1 cells caused a decrease in cell proliferation ( Figure 5 ). To explain these observations, other studies have reported that the binding of folic acid to its receptor can mediate a downstream signalling cascade that is able to inhibit the cellular survival processes including cell proliferation [ 28 , 29 ]. Our data are consistent with these reports.…”