SNAI2/Slug promotes growth and invasion in human gliomas.
SNAI2/Slug promotes growth and invasion in human gliomas.
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DOI：
10.1186/1471-2407-10-301
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发表时间：
2010-06-17
期刊：
影响因子：
3.8
通讯作者：
Johnson MD
中科院分区：
文献类型：
--
作者：
Yang HW;Menon LG;Black PM;Carroll RS;Johnson MD
已经确定了许多导致恶性胶质瘤侵袭的因素，但协调这一过程的上游基因知之甚少。为了确定控制胶质瘤侵袭的基因，我们使用原发人胶质瘤全基因组mRNA表达谱，建立了一个基于表达的30个转录因子的排序，这些转录因子先前涉及肿瘤侵袭和转移的调节。使用这种方法，我们确定了致癌转录抑制因子SNAI2/Slug在胶质母细胞瘤中过度表达的侵袭相关转录因子的前10%中。SNAI2 mRNA的表达与人原发性胶质瘤标本的组织学分级和侵袭性表型相关，并在人胶质瘤细胞中受EGF受体激活诱导。SNAI2/Slug的过表达增加了体外胶质母细胞瘤细胞的增殖和侵袭，促进了体内血管生成和胶质母细胞瘤的生长。重要的是，在小鼠颅内人胶质母细胞瘤移植模型中，在胶质母细胞瘤细胞中敲低内源性SNAI2/Slug可减少侵袭并提高存活率。这种基因组尺度的方法因此确定了SNAI2/Slug作为人类胶质瘤生长和侵袭的调节因子。
Numerous factors that contribute to malignant glioma invasion have been identified, but the upstream genes coordinating this process are poorly known. To identify genes controlling glioma invasion, we used genome-wide mRNA expression profiles of primary human glioblastomas to develop an expression-based rank ordering of 30 transcription factors that have previously been implicated in the regulation of invasion and metastasis in cancer. Using this approach, we identified the oncogenic transcriptional repressor, SNAI2/Slug, among the upper tenth percentile of invasion-related transcription factors overexpressed in glioblastomas. SNAI2 mRNA expression correlated with histologic grade and invasive phenotype in primary human glioma specimens, and was induced by EGF receptor activation in human glioblastoma cells. Overexpression of SNAI2/Slug increased glioblastoma cell proliferation and invasion in vitro and promoted angiogenesis and glioblastoma growth in vivo. Importantly, knockdown of endogenous SNAI2/Slug in glioblastoma cells decreased invasion and increased survival in a mouse intracranial human glioblastoma transplantation model. This genome-scale approach has thus identified SNAI2/Slug as a regulator of growth and invasion in human gliomas.
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影响因子：
50.3
作者：
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通讯作者：
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影响因子：
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DOI：
10.1097/01.jnen.0000248549.14962.b2
发表时间：
2006-12-01
影响因子：
3.2
作者：
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通讯作者：
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影响因子：
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影响因子：
11.2
作者：
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通讯作者：
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