Center for Laboratory Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, PR China.
Oncol Rep. 2012 Mar;27(3):819-24. doi: 10.3892/or.2011.1553. Epub 2011 Nov 15.
Histone deacetylase 6 (HDAC6) promotes cell motility and contributes to the metastasis of cancers. The purpose of this study was to investigate the role of HDAC6 in human bladder cancer for the first time. The results showed that HDAC6 promotes the migration and invasion of bladder cancer cells by targeting the cytoskeletal protein cortactin. Furthermore, a colony formation assay as well as in vitro migration and invasion assays demonstrated that this migration and invasion was suppressed by the HDAC6-specific inhibitor tubacin. In addition, cortactin is the substrate of SIRT2, which also belongs to the family of histone deacetylases. We demonstrated that by using SIRT2-specific siRNA combined with tubacin treatment, the cell migratory and invasive abilities were dramatically suppressed. Taken together, we conclude that HDAC6 and SIRT2 work synergistically to promote cell migration and invasion in bladder cancer, and the HDAC6-specific inhibitor tubacin may be regarded as a novel therapeutic agent for bladder cancer.
组蛋白去乙酰化酶 6（HDAC6）促进细胞迁移，有助于癌症转移。本研究的目的是首次研究 HDAC6 在人膀胱癌中的作用。结果表明，HDAC6 通过靶向细胞骨架蛋白 cortactin 促进膀胱癌细胞的迁移和侵袭。此外，集落形成实验以及体外迁移和侵袭实验表明，这种迁移和侵袭被 HDAC6 特异性抑制剂 tubacin 抑制。此外，cortactin 是 SIRT2 的底物，SIRT2 也属于组蛋白去乙酰化酶家族。我们通过使用 SIRT2 特异性 siRNA 与 tubacin 联合处理，证实细胞迁移和侵袭能力显著受到抑制。综上所述，我们得出结论，HDAC6 和 SIRT2 协同作用促进膀胱癌细胞迁移和侵袭，HDAC6 特异性抑制剂 tubacin 可能被视为膀胱癌的一种新型治疗药物。
