Role of fucosyltransferase IV in epithelial-mesenchymal transition in breast cancer cells.
Role of fucosyltransferase IV in epithelial-mesenchymal transition in breast cancer cells.
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DOI：
10.1038/cddis.2013.241
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发表时间：
2013-07-25
影响因子：
9
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中科院分区：
文献类型：
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上皮-间质转化（Epithelial-mesenchymal transition， EMT）是肿瘤进展的关键步骤，在肿瘤侵袭转移过程中起着重要作用。虽然focusyltransferase IV （FUT4）参与了细胞迁移、侵袭和癌症转移的调节，但其在EMT中的作用尚不清楚。本研究探讨了FUT4参与乳腺癌细胞EMT的分子机制。乳腺癌细胞系显示FUT4的表达增加，这伴随着间充质表型的增强，并且可以通过敲低内源性FUT4来逆转。此外，FUT4诱导磷脂酰肌醇3-激酶(PI3K)/Akt活化，GSK3β失活和NF-κB核易位，导致Snail和MMP-9表达增加，细胞运动性增强。综上所述，这些发现表明FUT4通过激活PI3K/Akt和NF-κB信号系统在EMT中发挥作用，这些信号系统诱导关键介质Snail和MMP-9，并促进间质表型的获得。我们的研究结果支持FUT4可能是乳腺癌细胞中EMT的一种新的调节因子，也是癌症治疗的一个有希望的靶点。
Epithelial–mesenchymal transition (EMT) is a crucial step in tumor progression and has an important role during cancer invasion and metastasis. Although fucosyltransferase IV (FUT4) has been implicated in the modulation of cell migration, invasion and cancer metastasis, its role during EMT is unclear. This study explores the molecular mechanisms of the involvement of FUT4 in EMT in breast cancer cells. Breast cancer cell lines display increased expression of FUT4, which is accompanied by enhanced appearance of the mesenchymal phenotype and which can be reversed by knockdown of endogenous FUT4. Moreover, FUT4 induced activation of phosphatidylinositol 3-kinase (PI3K)/Akt, and inactivation of GSK3β and nuclear translocation of NF-κB, resulting in increased Snail and MMP-9 expression and greater cell motility. Taken together, these findings indicate that FUT4 has a role in EMT through activation of the PI3K/Akt and NF-κB signaling systems, which induce the key mediators Snail and MMP-9 and facilitate the acquisition of a mesenchymal phenotype. Our findings support the possibility that FUT4 is a novel regulator of EMT in breast cancer cells and a promising target for cancer therapy.