The DEAD/DEAH box helicase, DDX11, is essential for the survival of advanced melanomas.
The DEAD/DEAH box helicase, DDX11, is essential for the survival of advanced melanomas.
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DOI：
10.1186/1476-4598-11-82
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发表时间：
2012-11-01
期刊：
影响因子：
37.3
通讯作者：
Becker D
中科院分区：
文献类型：
--
作者：
Bhattacharya C;Wang X;Becker D
尽管不断努力确定哪些基因是晚期黑色素瘤的关键调节基因并与其密切相关，并确定这些基因中的哪些在功能上必须被阻断以控制这种高度侵袭性的疾病，但目前还远不清楚哪种分子途径(S)和其中的特定基因是原发和转移性黑色素瘤的阿喀琉斯之踵。在这份报告中，我们提供了一些数据，这些数据证明了死盒解旋酶DDX11是黑色素瘤细胞生存的关键守门人，它是姐妹染色单体凝聚所必需的。通过免疫组织化学和免疫印迹分析，我们检测了DDX11在黑色素瘤组织和细胞系中的表达。在用DDX11特异性siRNA转染黑色素瘤细胞后，我们进行了qPCR分析，以确定DDX11在转染组黑色素瘤细胞中的下调。在随后的研究中，我们确定了抑制DDX11表达对代表晚期黑色素瘤的黑色素瘤细胞的影响，这些研究集中在荧光标记的分析以及Giesma染色的染色体扩散、增殖分析和凋亡分析上。本文提出的研究结果表明，DDX11在从非侵袭性黑色素瘤向侵袭性黑色素瘤进展过程中上调，并且在晚期黑色素瘤中高水平表达。此外，同样重要的是，我们证明了阻断DDX11的表达不仅会抑制黑色素瘤细胞的增殖和严重的染色体分离缺陷，而且还会迅速导致黑色素瘤细胞大量凋亡。到目前为止，关于解旋酶是否在黑色素瘤的发展中发挥作用，特别是在从早期黑色素瘤到晚期黑色素瘤的进展过程中，人们知之甚少。在这份报告中，我们发现解旋酶DDX11在原发和转移性黑色素瘤中高水平表达，干扰其表达会导致严重的染色体分离缺陷、端粒缩短和黑色素瘤细胞大量凋亡。这些发现表明，DDX11可能是晚期黑色素瘤分子靶向治疗的重要候选基因。
Despite continuous efforts to identify genes that are pivotal regulators of advanced melanoma and closely related to it, to determine which of these genes have to be blocked in their function to keep this highly aggressive disease in check, it is far from clear which molecular pathway(s) and specific genes therein, is the Achilles’ heel of primary and metastatic melanoma. In this report, we present data, which document that the DEAD-box helicase DDX11, which is required for sister chromatid cohesion, is a crucial gatekeeper for melanoma cell survival. Performing immunohistochemistry and immunoblot analysis, we determined expression of DDX11 in melanoma tissues and cell lines. Following transfection of melanoma cells with a DDX11-specific siRNA, we conducted a qPCR analysis to determine downregulation of DDX11 in the transfected melanoma cells. In subsequent studies, which focused upon an analysis of fluorescently labeled as well as Giesma-stained chromosome spreads, a proliferation analysis and apoptosis assays, we determined the impact of suppressing DDX11 expression on melanoma cells representing advanced melanoma. The findings of the study presented herein document that DDX11 is upregulated with progression from noninvasive to invasive melanoma, and that it is expressed at high levels in advanced melanoma. Furthermore, and equally important, we demonstrate that blocking the expression of DDX11 leads not only to inhibition of melanoma cell proliferation and severe defects in chromosome segregation, but also drives melanoma cells rapidly into massive apoptosis. To date, little is known as to whether helicases play a role in melanoma development and specifically, in the progression from early to advanced melanoma. In this report, we show that the helicase DDX11 is expressed at high levels in primary and metastatic melanoma, and that interfering with its expression leads to severe chromosome segregation defects, telomere shortening, and massive melanoma cell apoptosis. These findings suggest that DDX11 could be an important candidate for molecular targeted therapy for advanced melanoma.
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影响因子：
9.8
作者：
Vasa-Nicotera, M;Brouilette, S;Samani, NJ
通讯作者：
Samani, NJ
髓母细胞瘤外观测序发现亚型特异性体细胞突变。
影响因子：
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Cho, Yoon-Jae
影响因子：
4.3
作者：
Abdullah, Christopher;Wang, Xiaolei;Becker, Dorothea
通讯作者：
Becker, Dorothea
影响因子：
14.9
作者：
Hirota, Y;Lahti, JM
通讯作者：
Lahti, JM
影响因子：
4.8
作者：
Farina, Andrea;Shin, Jae-Ho;Hurwitz, Jerard
通讯作者：
Hurwitz, Jerard