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Histone deacetylase 6 (HDAC6) promotes cell motility and contributes tothe metastasis of cancers. The purpose of this study was to investigate the roleof HDAC6 in human bladder cancer for the first time. The results showed that HDAC6promotes the migration and invasion of bladder cancer cells by targeting the cytoskeletalprotein cortactin. Furthermore, a colony formation assay as well as in vitro migrationand invasion assays demonstrated that this migration and invasion was suppressedby the HDAC6-specific inhibitor tubacin. In addition, cortactin is the substrateof SIRT2, which also belongs to the family of histone deacetylases. We demonstratedthat by using SIRT2-specific siRNA combined with tubacin treatment, the cell migratoryand invasive abilities were dramatically suppressed. Taken together, we concludethat HDAC6 and SIRT2 work synergistically to promote cell migration and invasionin bladder cancer, and the HDAC6-specific inhibitor tubacin may be regarded asa novel therapeutic agent for bladder cancer.

HDAC6 and SIRT2 promote bladder cancer cell migration and invasion by targeting cortactin