Role of the ST6GAL1 sialyltransferase in regulating ovarian cancer cell metabolism.
Role of the ST6GAL1 sialyltransferase in regulating ovarian cancer cell metabolism.
复制标题
ST6GAL1唾液酸转移酶在调节卵巢癌细胞代谢中的作用。
DOI：
10.1093/glycob/cwad051
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发表时间：
2023
期刊：
影响因子：
4.3
通讯作者：
Bellis,SusanL
中科院分区：
文献类型：
--
作者：
Jones,RobertB;Silva,AustinD;Ankenbauer,KatherineE;Britain,ColleenM;Chakraborty,Asmi;Brown,JamelleA;Ballinger,ScottW;Bellis,SusanL
ST 6 GAL 1唾液酸转移酶将α2-6-连接的唾液酸添加到N-糖基化蛋白，在许多恶性肿瘤包括卵巢癌中上调。通过其唾液酸化选择表面受体的活性，ST 6 GAL 1调节细胞内信号传导以调节肿瘤细胞表型。ST 6 GAL 1先前已被证明是一种存活因子，可保护癌细胞免受细胞毒性应激因素（如缺氧）的影响。在本研究中，我们研究了ST 6 GAL 1在肿瘤细胞代谢中的作用。ST 6 GAL 1在具有低内源性ST 6 GAL 1的OV 4卵巢癌细胞中过表达（OE），或在具有高内源性ST 6 GAL 1的ID 8卵巢癌细胞中敲低（KD）。使具有调节的ST 6 GAL 1表达的OV 4和ID 8细胞在常氧或低氧条件下生长，并使用Seahorse技术评估代谢。结果显示，ST 6 GAL 1高表达的细胞在用低氧模拟物去铁胺（DFO）处理后保持比对照细胞更高的氧化代谢速率。这种富集不是由于线粒体数量的增加。糖酵解代谢也增加了OV 4和ID 8细胞与高ST 6 GAL 1表达，这些细胞显示出更大的活性的糖酵解酶，己糖激酶和磷酸果糖激酶。从组合的Seahorse数据生成代谢图，这表明ST 6 GAL 1的功能是增强肿瘤细胞的整体代谢。最后，我们确定具有高ST 6 GAL 1表达的OV 4和ID 8细胞在缺氧条件下更具侵袭性。总的来说，这些结果突出了唾液酸化在调节卵巢癌细胞代谢表型中的重要性。
The ST6GAL1 sialyltransferase, which adds α2–6-linked sialic acids toN-glycosylated proteins, is upregulated in many malignancies including ovarian cancer. Through its activity in sialylating select surface receptors, ST6GAL1 modulates intracellular signaling to regulate tumor cell phenotype. ST6GAL1 has previously been shown to act as a survival factor that protects cancer cells from cytotoxic stressors such as hypoxia. In the present study, we investigated a role for ST6GAL1 in tumor cell metabolism. ST6GAL1 was overexpressed (OE) in OV4 ovarian cancer cells, which have low endogenous ST6GAL1, or knocked-down (KD) in ID8 ovarian cancer cells, which have high endogenous ST6GAL1. OV4 and ID8 cells with modulated ST6GAL1 expression were grown under normoxic or hypoxic conditions, and metabolism was assessed using Seahorse technology. Results showed that cells with high ST6GAL1 expression maintained a higher rate of oxidative metabolism than control cells following treatment with the hypoxia mimetic, desferrioxamine (DFO). This enrichment was not due to an increase in mitochondrial number. Glycolytic metabolism was also increased in OV4 and ID8 cells with high ST6GAL1 expression, and these cells displayed greater activity of the glycolytic enzymes, hexokinase and phosphofructokinase. Metabolism maps were generated from the combined Seahorse data, which suggested that ST6GAL1 functions to enhance the overall metabolism of tumor cells. Finally, we determined that OV4 and ID8 cells with high ST6GAL1 expression were more invasive under conditions of hypoxia. Collectively, these results highlight the importance of sialylation in regulating the metabolic phenotype of ovarian cancer cells.