Aberrant overexpression of the cell polarity module scribble in human cancer.
Aberrant overexpression of the cell polarity module scribble in human cancer.
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DOI：
10.1016/j.ajpath.2011.02.028
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发表时间：
2011-06
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影响因子：
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通讯作者：
V. Vaira;Alice Faversani;T. Dohi;M. Maggioni;M. Nosotti;D. Tosi;D. Altieri;S. Bosari
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文献类型：
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作者：
V. Vaira;Alice Faversani;T. Dohi;M. Maggioni;M. Nosotti;D. Tosi;D. Altieri;S. Bosari
Human Scribble (Scrib) 是一种进化保守的细胞极性蛋白，但其在人类癌症中的潜在作用存在争议。在此，我们表明，与体内匹配的正常组织相比，Scrib 在培养的肿瘤细胞系和遗传不同的癌症患者系列中几乎普遍过度表达。与正常上皮细胞中看到的膜关联不同，肿瘤相关的 Scrib 定位错误，主要存在于细胞质中。在模型肺腺癌 A549 细胞中，Scrib 的小干扰 RNA 沉默可抑制伤口愈合试验中的细胞迁移，抑制肿瘤细胞侵入基质胶包被的插入物，并下调细胞运动标记物和上皮间质转化介质的表达。这些数据揭示了之前未被认识到的 Scrib 对异常肿瘤细胞运动和侵袭的利用，从而可能导致人类疾病进展。
Human Scribble (Scrib) is an evolutionary-conserved cell polarity protein, but its potential role in human cancer is controversial. Herein, we show that Scrib is nearly universally overexpressed in cultured tumor cell lines and genetically disparate cancer patient series compared with matched normal tissuesin vivo. Instead of a membrane association seen in normal epithelia, tumor-associated Scrib is mislocalized and found predominantly in the cytosol. Small-interfering RNA silencing of Scrib in model lung adenocarcinoma A549 cells inhibited cell migration in wound-healing assays, suppressed tumor cell invasion across Matrigel-coated inserts, and down-regulated the expression of cell motility markers and mediators of epithelial-mesenchymal transition. These data uncover a previously unrecognized exploitation of Scrib for aberrant tumor cell motility and invasion, thus potentially contributing to disease progression in humans.