Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX, USA.
Sci Rep. 2019 Nov 22;9(1):17361. doi: 10.1038/s41598-019-53984-8.
Breast cancer brain metastasis has been recognized as one of the central issues in breast cancer research. The elucidation of the processes and pathways that mediate this step will provide important clues for a better understanding of breast cancer metastasis. Increasing evidence suggests that aberrant glycosylation patterns greatly contribute to cell invasion and cancer metastasis. Herein, we combined next-generation RNA sequencing with liquid chromatography-tandem mass spectrometry-based proteomic and N-glycomic analysis from five breast cancer cell lines and one brain cancer cell line to investigate the possible mechanisms of breast cancer brain metastasis. The genes/proteins associated with cell movement were highlighted in breast cancer brain metastasis. The integrin signaling pathway and the up-regulation of α-integrin (ITGA2, ITGA3) were associated with the brain metastatic process. 12 glycogenes showed unique expression in 231BR, which could result in an increase of sialylation during brain metastasis. In agreement with the changes of glycogenes, 60 out of 63 N-glycans that were identified exhibited differential expression among cell lines. The correlation between glycogenes and glycans revealed the importance of sialylation and sialylated glycans in breast cancer brain metastasis. Highly sialylated N-glycans, which were up-regulated in brain-seeking cell line 231BR, likely play a role in brain metastasis.
乳腺癌脑转移已被认为是乳腺癌研究的核心问题之一。阐明介导这一过程的过程和途径将为更好地理解乳腺癌转移提供重要线索。越来越多的证据表明，异常的糖基化模式极大地促进了细胞侵袭和癌症转移。在此，我们结合下一代 RNA 测序与来自五株乳腺癌细胞系和一株脑癌细胞系的基于液相色谱-串联质谱的蛋白质组学和 N-糖组学分析，研究乳腺癌脑转移的可能机制。与细胞运动相关的基因/蛋白在乳腺癌脑转移中被突出显示。整合素信号通路和 α-整合素（ITGA2、ITGA3）的上调与脑转移过程相关。12 个糖基因在 231BR 中表现出独特的表达，这可能导致脑转移过程中唾液酸化增加。与糖基因的变化一致，在细胞系中鉴定出的 63 个 N-聚糖中有 60 个表现出差异表达。糖基因和聚糖之间的相关性揭示了唾液酸化和唾液酸化聚糖在乳腺癌脑转移中的重要性。在寻找大脑的细胞系 231BR 中上调的高度唾液酸化的 N-聚糖可能在脑转移中发挥作用。
