Department of Breast Surgery, The Third Hospital of Nanchang, Jiangxi Provincial-Key-Laboratory for Breast Diseases, Jiangxi Province, 330006, China.
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
Biochem Biophys Res Commun. 2018 Nov 30;506(3):563-570. doi: 10.1016/j.bbrc.2018.10.109. Epub 2018 Oct 23.
FAT10, an ubiquitin-like protein, functions as a potential tumor promoter in several caners. However, the function and clinical significance of FAT10 in breast cancer (BC) remains unclear. Here, we found that high FAT10 expression was detected frequently in primary BC tissues, and was closely associated with malignant phenotype and shorter survival among the BC patients. Multivariate analyses also revealed that FAT10 overexpression was independent prognostic factors for poor outcome of patients with BC. Function assay demonstrated that FAT10 knockdown significantly inhibited the metastasis abilities and the epithelial-mesenchymal transition (EMT) of breast cancer cell. Further investigation revealed that FAT10 directly bound ZEB2 and decreased its ubiquitination to enhance the protein stability of ZEB2 in BC cells. Moreover, our data shown that the pro-metastasis effect of FAT10 in BC is partially dependent on ZEB2 enhancement. Collectively, our data suggest that FAT10 plays a crucial oncogenic role in BC metastasis, and we provide a novel evidence that FAT10 may be serve as a prognostic and therapeutic target for BC patients.
FAT10 是一种泛素样蛋白，在几种癌症中作为潜在的肿瘤促进因子发挥作用。然而，FAT10 在乳腺癌（BC）中的功能和临床意义尚不清楚。在这里，我们发现 FAT10 高表达在原发性 BC 组织中经常被检测到，并与 BC 患者的恶性表型和更短的生存时间密切相关。多因素分析还表明，FAT10 过表达是 BC 患者预后不良的独立预后因素。功能分析表明，FAT10 敲低显著抑制了乳腺癌细胞的转移能力和上皮-间充质转化（EMT）。进一步的研究表明，FAT10 直接与 ZEB2 结合，并减少其泛素化，以增强 BC 细胞中 ZEB2 的蛋白稳定性。此外，我们的数据表明，FAT10 在 BC 中的促转移作用部分依赖于 ZEB2 的增强。总之，我们的数据表明 FAT10 在 BC 转移中发挥着关键的致癌作用，我们提供了新的证据表明 FAT10 可能成为 BC 患者的预后和治疗靶点。
