Hongqiao Institute of Medicine, Tongren Hospital/Faculty of Basic Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Breast Cancer Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Cell Death Dis. 2023 Apr 24;14(4):288. doi: 10.1038/s41419-023-05797-x.
Snail is a denoted transcriptional repressor that plays key roles in epithelial-mesenchymal transition (EMT) and metastasis. Lately, a plethora of genes can be induced by stable expression of Snail in multiple cell lines. However, the biological roles of these upregulated genes are largely elusive. Here, we report identification of a gene encoding the key GlcNAc sulfation enzyme CHST2 is induced by Snail in multiple breast cancer cells. Biologically, CHST2 depletion results in inhibition of breast cancer cell migration and metastasis, while overexpression of CHST2 promotes cell migration and lung metastasis in nude mice. In addition, the expression level of MECA79 antigen is elevated and blocking the cell surface MECA79 antigen with specific antibodies can override cell migration mediated by CHST2 upregulation. Moreover, the sulfation inhibitor sodium chlorate effectively inhibits the cell migration induced by CHST2. Collectively, these data provide novel insights into the biology of Snail/CHST2/MECA79 axis in breast cancer progression and metastasis as well as potential therapeutic strategy for the diagnosis and treatment of breast cancer metastasis.
蜗牛是一种被标记的转录抑制因子，在上皮-间充质转化（EMT）和转移中发挥关键作用。最近，在多种细胞系中稳定表达蜗牛可以诱导大量基因。然而，这些上调基因的生物学作用在很大程度上还不清楚。在这里，我们报告了一种基因的鉴定，该基因编码关键的 GlcNAc 硫酸化酶 CHST2，在多种乳腺癌细胞中被蜗牛诱导。从生物学上讲，CHST2 的缺失导致乳腺癌细胞迁移和转移的抑制，而 CHST2 的过表达则促进裸鼠中的细胞迁移和肺转移。此外，MECA79 抗原的表达水平升高，并且用特异性抗体阻断细胞表面的 MECA79 抗原可以克服由 CHST2 上调介导的细胞迁移。此外，硫酸化抑制剂氯酸钠可有效抑制 CHST2 诱导的细胞迁移。总之，这些数据为乳腺癌进展和转移中蜗牛/CHST2/MECA79 轴的生物学提供了新的见解，以及用于诊断和治疗乳腺癌转移的潜在治疗策略。
