Doud Emma H, Shetty Trupti, Abt Melissa, Mosley Amber L, Corson Timothy W, Mehta Anand, Yeh Elizabeth S
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Biomedicines. 2020 Dec 12;8(12):600. doi: 10.3390/biomedicines8120600.
A growing body of evidence indicates that the levels of fucosylation correlate with breast cancer progression and contribute to metastatic disease. However, very little is known about the signaling and functional outcomes that are driven by fucosylation. We performed a global proteomic analysis of 4T1 metastatic mammary tumor cells in the presence and absence of a fucosylation inhibitor, 2-fluorofucose (2FF). Of significant interest, pathway analysis based on our results revealed a reduction in the NF-κB and TNF signaling pathways, which regulate the inflammatory response. NF-κB is a transcription factor that is pro-tumorigenic and a prime target in human cancer. We validated our results, confirming that treatment of 4T1 cells with 2FF led to a decrease in NF-κB activity through increased IκBα. Based on these observations, we conclude that fucosylation is an important post-translational modification that governs breast cancer cell signaling.
越来越多的证据表明，岩藻糖基化水平与乳腺癌进展相关，并促进转移性疾病。然而，对于岩藻糖基化驱动的信号传导和功能结果知之甚少。我们对4T1转移性乳腺肿瘤细胞在存在和不存在岩藻糖基化抑制剂2-氟岩藻糖（2FF）的情况下进行了全蛋白质组分析。值得关注的是，基于我们的结果进行的通路分析显示，调节炎症反应的NF-κB和TNF信号通路有所减少。NF-κB是一种具有促肿瘤作用的转录因子，也是人类癌症的主要靶点。我们验证了我们的结果，证实用2FF处理4T1细胞会通过增加IκBα导致NF-κB活性降低。基于这些观察结果，我们得出结论，岩藻糖基化是一种重要的翻译后修饰，可调控乳腺癌细胞信号传导。
