Guo Dong, Guo Jia, Li Xiang, Guan Feng
1 The Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
2 Wuxi Medical School, Jiangnan University, Wuxi 214122, China.
Exp Biol Med (Maywood). 2017 Jan;242(2):177-183. doi: 10.1177/1535370216669838. Epub 2016 Oct 4.
Glycosylation of certain proteins at the mammalian cell surface is an essential event in carcinogenesis. Sialylation, one type of glycosylation, can act on multiple cell-behaviors, such as migration, growth, and malignant invasion. Two polysialyltransferases, ST8Sia II (STX) and ST8Sia IV (PST), are responsible for synthesis of polysialic acid on neural cell adhesion molecule. We showed previously that STX and PST are oppositely expressed in normal murine mammary gland cells undergoing transforming growth factor-β-induced epithelial-mesenchymal transition. The molecular basis for regulation of STX and PST remained unclear. In the present study, we observed that transcription factor Pax3 upregulates STX expression, downregulates PST expression, and modulates upregulated expression of PSA, which attaches primarily to neural cell adhesion molecule to form PSA-NCAM. Overexpression of Pax3 in normal murine mammary gland cells transformed the expression of epithelial-mesenchymal transition markers E-cadherin and N-cadherin, and significantly promoted cell migration, but had no effect on cell proliferation.
哺乳动物细胞表面某些蛋白质的糖基化是致癌过程中的一个重要事件。唾液酸化作为糖基化的一种类型,可作用于多种细胞行为,如迁移、生长和恶性侵袭。两种多唾液酸转移酶,即ST8Sia II(STX)和ST8Sia IV(PST),负责在神经细胞黏附分子上合成多唾液酸。我们之前表明,在经历转化生长因子-β诱导的上皮-间质转化的正常小鼠乳腺细胞中,STX和PST的表达呈相反状态。STX和PST调控的分子基础仍不清楚。在本研究中,我们观察到转录因子Pax3上调STX表达,下调PST表达,并调节主要附着于神经细胞黏附分子以形成PSA-NCAM的PSA的上调表达。Pax3在正常小鼠乳腺细胞中的过表达改变了上皮-间质转化标志物E-钙黏蛋白和N-钙黏蛋白的表达,并显著促进细胞迁移,但对细胞增殖没有影响。