Turner David P, Moussa Omar, Sauane Moira, Fisher Paul B, Watson Dennis K
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Cancer Res. 2007 Feb 15;67(4):1618-25. doi: 10.1158/0008-5472.CAN-06-2913.
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.
细胞迁移和侵袭是肿瘤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，穿透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）在人侵袭性乳腺组织中的表达降低，在侵袭性乳腺癌细胞系中则缺失。研究细胞迁移不同方面的功能获得性研究表明，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，而功能缺失性研究表明，非侵袭性乳腺癌细胞的迁移会受到刺激。此外，将PDEF导入侵袭性乳腺癌细胞会导致肌动蛋白细胞骨架重塑，并改变粘着斑的定位和粘附水平。表达PDEF的细胞不再形成高效定向迁移所需的明确形态极性。总体而言，这些数据表明，侵袭性乳腺癌中PDEF的下调可能通过细胞外基质促进肌动蛋白介导的细胞迁移。
