Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China.
National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China.
J Hematol Oncol. 2018 Sep 3;11(1):111. doi: 10.1186/s13045-018-0654-9.
Histone acetylation and deacetylation are important epigenetic mechanisms that regulate gene expression and transcription. Histone deacetylase 6 (HDAC6) is a unique member of the HDAC family that not only participates in histone acetylation and deacetylation but also targets several nonhistone substrates, such as α-tubulin, cortactin, and heat shock protein 90 (HSP90), to regulate cell proliferation, metastasis, invasion, and mitosis in tumors. Furthermore, HDAC6 also upregulates several critical factors in the immune system, such as program death receptor-1 (PD-1) and program death receptor ligand-1 (PD-L1) receptor, which are the main targets for cancer immunotherapy. Several selective HDAC6 inhibitors are currently in clinical trials for cancer treatment and bring hope for patients with malignant tumors. A fuller understanding of HDAC6 as a critical regulator of many cellular pathways will help further the development of targeted anti-HDAC6 therapies. Here, we review the unique features of HDAC6 and its role in cancer, which make HDAC6 an appealing drug target.
组蛋白乙酰化和去乙酰化是重要的表观遗传机制，可调节基因表达和转录。组蛋白去乙酰化酶 6（HDAC6）是 HDAC 家族中的一个独特成员，它不仅参与组蛋白乙酰化和去乙酰化，还靶向几种非组蛋白底物，如α-微管蛋白、皮质蛋白和热休克蛋白 90（HSP90），以调节肿瘤中的细胞增殖、转移、侵袭和有丝分裂。此外，HDAC6 还上调免疫系统中的几个关键因子，如程序性死亡受体-1（PD-1）和程序性死亡受体配体-1（PD-L1）受体，它们是癌症免疫治疗的主要靶点。几种选择性 HDAC6 抑制剂目前正在临床试验中用于癌症治疗，为恶性肿瘤患者带来了希望。更全面地了解 HDAC6 作为许多细胞途径的关键调节剂将有助于进一步开发靶向抗 HDAC6 治疗方法。在这里，我们回顾了 HDAC6 的独特特征及其在癌症中的作用，这使其成为一个有吸引力的药物靶点。
