Prostate-derived ETS factor is a mediator of metastatic potential through the inhibition of migration and invasion in breast cancer
Prostate-derived ETS factor is a mediator of metastatic potential through the inhibition of migration and invasion in breast cancer
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DOI：
10.1158/0008-5472.can-06-2913
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发表时间：
2007-02-15
期刊：
影响因子：
11.2
通讯作者：
Watson, Dennis K.
中科院分区：
文献类型：
--
作者：
Turner, David P.;Moussa, Omar;Watson, Dennis K.
细胞迁移和侵袭是转移过程中的关键事件。如果没有运动功能，癌细胞就无法离开原发肿瘤部位，侵入基底膜并形成继发性肿瘤。上皮特异性 ETS 因子前列腺源性 ETS 因子 (PDEF) 的表达在人类侵袭性乳腺组织中减少，并在侵袭性乳腺癌细胞系中丢失。检查细胞迁移不同方面的功能获得研究表明，组成型或诱导型 PDEF 重新表达可抑制多种乳腺癌细胞系的迁移和侵袭，而功能丧失研究则表明可刺激非侵袭性乳腺癌细胞的迁移。此外，将PDEF引入侵袭性乳腺癌细胞导致肌动蛋白细胞骨架的重塑并改变粘着斑定位和粘附水平。表达 PDEF 的细胞不再形成有效、定向迁移所需的确定的形态极性。总的来说，这些数据表明侵袭性乳腺癌中 PDEF 的下调可能会促进肌动蛋白介导的细胞通过细胞外基质的迁移。
Cell migration and invasion are critical events during the progression to metastasis. Without motile function, cancer cells are unable to leave the primary tumor site, invade through the basement membrane, and form secondary tumors. Expression of the epithelial-specific ETS factor prostate-derived ETS factor (PDEF) is reduced in human invasive breast tissue and lost in invasive breast cancer cell lines. Gain-of-function studies that examine different aspects of cell migration show that constitutive or inducible PDEF reexpression inhibits migration and invasion in multiple breast cancer cell lines, and loss-of-function studies show a stimulation of migration in noninvasive breast cancer cells. Furthermore, the introduction of PDEF into invasive breast cancer cells led to a remodeling of the actin cytoskeleton and altered focal adhesion localization and adherence levels. Cells expressing PDEF no longer form the defined morphologic polarity required for efficient, directional migration. Collectively, these data indicate that PDEF down-regulation in invasive breast cancer may promote actin-mediated cell migration through the extracellular matrix.