Department of Otorhinolaryngology - Head and Neck Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
Department of Otorhinolaryngology - Head and Neck Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
Biosci Rep. 2017 Dec 5;37(6). doi: 10.1042/BSR20170772. Print 2017 Dec 22.
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.
叶酸（FA）是哺乳动物正常细胞分裂所必需的，已被认为与许多肿瘤有关。据报道，膳食 FA 摄入与鼻咽癌（NPC）的风险降低有关。然而，FA 在 NPC 细胞中的分子机制仍不清楚。在本研究中，我们发现 FA 通过叶酸受体α（FRα）剂量依赖性地抑制 NPC 细胞的增殖、侵袭和迁移。我们进一步发现，与 FRα 结合的 FA 诱导 MEK/ERK1/2 的激活，并增加 TSLC1 和 E-钙粘蛋白的表达。此外，阻断 ERK1/2 的激活可减弱 FA 介导的 TSLC1 表达增加。此外，敲低 TSLC1 可消除 FA 介导的 NPC 细胞增殖、侵袭和迁移抑制，并抑制 FA 介导的 E-钙粘蛋白表达增加。总之，我们的数据表明，FA 通过激活 FRα/ERK1/2/TSLC1 信号通路抑制 NPC 细胞的增殖和侵袭。因此，FA 可作为治疗 NPC 的治疗药物进行探索，TSLC1 可能在 NPC 中作为肿瘤抑制因子发挥作用。
