2012年8月30日 讯 /生物谷BIOON/ --凝溶胶蛋白是一种细胞骨架蛋白，具有提高细胞活力和可塑性的功效。凝溶胶蛋白（Gelsolin）是凝溶胶蛋白超家族的成员之一，是一种重要的肌动蛋白结合蛋白，其通过切断、封端肌动蛋白丝，或使肌动蛋白聚集成核等方式来控制肌动蛋白的结构。凝溶胶蛋白除了在重组肌动蛋白丝中发挥作用以外，还在细胞运动、控制细胞程序性死亡等细胞活动中发挥重要的作用。此外，肿瘤细胞中凝溶胶蛋白的表达量也发生变化。凝溶胶蛋白的变异还是某些遗传疾病的基础。
虽然最初认为凝溶胶蛋白是一种肿瘤抑制基因，但最新研究发现凝溶胶蛋白在某些肿瘤中的表达与预后差相关。在体外，凝溶胶蛋白具有抗凋亡和迁移的功能，并且对是某些类型肿瘤细胞的侵袭是至关重要的。
用免疫组化检查，科研人员发凝溶胶蛋白在侵入肝器官中的癌组织边界中高表达。虽然凝溶胶蛋白对细胞迁移过程中片状伪足的形成，诱导肿瘤的侵袭有贡献，但目前还不清楚其中明确机制。使用过表达技术和RNA干扰技术过表达或是敲除大肠癌细胞中凝溶胶蛋白的表达后，研究人员考察了凝溶胶蛋白对侵袭能力的影响。
研究表明，凝溶胶蛋白对大肠癌细胞侵入基底膜是必须的。微阵列分析和定量PCR研究表明，凝溶胶蛋白的过度表达引起的促进大肠癌的肿瘤细胞中侵袭基因表达上调，这其中包括降解基质的尿激酶型纤溶酶原激活剂（uPA）。
相反，凝溶胶蛋白被抑制后，uPA的表达水平也会降低，uPA的分泌也受到相应的抑制。凝溶胶蛋白过度表达的肿瘤细胞用特异性的uPA或其受体抗体阻断后侵袭能减弱，可见uPA/及其受体uPAR对凝溶胶蛋白促进肿瘤细胞侵袭是至关重要的。总之，研究数据证实凝溶胶蛋白通过调节uPA/uPAR信号级联促进大肠癌肿瘤细胞的侵袭。相关研究论文发表在PLoS One杂志上。（生物谷：Bioon.com）
doi:10.1371/journal.pone.0043594
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Gelsolin Induces Colorectal Tumor Cell Invasion via Modulation of the Urokinase-Type Plasminogen Activator Cascade.
Zhuo, J., E. H. Tan, et al.
Gelsolin is a cytoskeletal protein which participates in actin filament dynamics and promotes cell motility and plasticity. Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells. We found that gelsolin was highly expressed at tumor borders infiltrating into adjacent liver tissues, as examined by immunohistochemistry. Although gelsolin contributes to lamellipodia formation in migrating cells, the mechanisms by which it induces tumor invasion are unclear. Gelsolin's influence on the invasive activity of colorectal cancer cells was investigated using overexpression and small interfering RNA knockdown. We show that gelsolin is required for invasion of colorectal cancer cells through matrigel. Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion. The enhanced invasiveness of gelsolin-overexpressing cells was attenuated by treatment with function-blocking antibodies to either uPA or its receptor uPAR, indicating that uPA/uPAR activity is crucial for gelsolin-dependent invasion. In summary, our data reveals novel functions of gelsolin in colorectal tumor cell invasion through its modulation of the uPA/uPAR cascade, with potentially important roles in colorectal tumor dissemination to metastatic sites.
