HDAC6 regulates neuroblastoma cell migration and may play a role in the invasion process
HDAC6 regulates neuroblastoma cell migration and may play a role in the invasion process
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HDAC6 调节神经母细胞瘤细胞迁移并可能在侵袭过程中发挥作用
DOI：
10.4161/15384047.2014.956632
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
李登文
中科院分区：
文献类型：
--
作者：
李登文
神经母细胞瘤是最常见的儿童颅外实体瘤之一，通常在发生播散后才被诊断。尽管最近在这种恶性肿瘤的多模式治疗方面取得了进展，但其治疗效果仍然很差。因此，非常需要新的治疗策略。在此，我们证明组蛋白脱乙酰酶6（HDAC6），主要位于细胞质中的脱乙酰酶家族的成员，参与神经母细胞瘤的传播。HDAC6在神经母细胞瘤组织样本中的表达随肿瘤部位而变化。HDAC 6对神经母细胞瘤细胞的增殖几乎没有影响。相反，通过RNA干扰下调HDAC6表达或通过药理学抑制剂tubacin抑制其催化活性显著降低了3种人恶性神经母细胞瘤细胞系的迁移，并降低了3种细胞系之一的侵袭能力，但对人正常脑胶质细胞的迁移和侵袭只有轻微影响。我们的数据进一步揭示了HDAC 6对神经母细胞瘤细胞迁移的调节是通过其对细胞极化和粘附的影响介导的。这些发现表明HDAC 6在神经母细胞瘤传播中发挥作用，并且有可能使用HDAC 6抑制剂来治疗这种恶性肿瘤。
Neuroblastoma is one of the most prevalent pediatric extracranial solid tumors and is often diagnosed after dissemination has occurred. Despite recent advances in multimodal therapies of this malignancy, its therapeutic efficacy remains poor. Novel treatment strategies are thus in great need. Herein, we demonstrate that histone deacetylase 6 (HDAC6), a member of the deacetylase family that is localized predominantly in the cytoplasm, is involved in neuroblastoma dissemination. HDAC6 expression in neuroblastoma tissue samples varied with the site of the tumor. HDAC6 showed little impact on the proliferation of neuroblastoma cells. Instead, downregulation of HDAC6 expression by RNA interference or inhibition of its catalytic activity by the pharmacological inhibitor tubacin significantly decreased the migration of 3 human malignant neuroblastoma cell lines and reduced the invasion ability of one of the 3 cell lines, but only slightly affected the migration and invasion of human normal brain glial cells. Our data further revealed that the regulation of neuroblastoma cell migration by HDAC6 was mediated by its effects on cell polarization and adhesion. These findings suggest a role for HDAC6 in neuroblastoma dissemination and a potential of using HDAC6 inhibitors for the treatment of this malignancy.
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影响因子：
--
作者：
Aldana-Masangkay GI;Sakamoto KM
通讯作者：
Sakamoto KM
影响因子：
64.8
作者：
Hubbert, C;Guardiola, A;Yao, TP
通讯作者：
Yao, TP
DOI：
10.1016/s1387-2656(05)11004-7
发表时间：
2005-01-01
期刊：
BIOTECHNOLOGY ANNUAL REVIEW, VOL 11
影响因子：
--
作者：
Berridge, MV;Herst, PM;Tan, AS
通讯作者：
Tan, AS
影响因子：
4.8
作者：
Subramanian, Chitra;Jarzembowski, Jason A.;Kwok, Roland P. S.
通讯作者：
Kwok, Roland P. S.
影响因子：
5.2
作者：
Takumi Sakuma;K. Uzawa;Takeshi Onda;M. Shiiba;H. Yokoe;T. Shibahara;H. Tanzawa
通讯作者：
Takumi Sakuma;K. Uzawa;Takeshi Onda;M. Shiiba;H. Yokoe;T. Shibahara;H. Tanzawa