2012年8月30日 訊 /生物谷BIOON/ --凝溶膠蛋白是一種細胞骨架蛋白,，具有提高細胞活力和可塑性的功效,。凝溶膠蛋白（Gelsolin）是凝溶膠蛋白超家族的成員之一，是一種重要的肌動蛋白結合蛋白,，其通過切斷,、封端肌動蛋白絲，或使肌動蛋白聚集成核等方式來控制肌動蛋白的結構,。凝溶膠蛋白除了在重組肌動蛋白絲中發(fā)揮作用以外,，還在細胞運動、控制細胞程序性死亡等細胞活動中發(fā)揮重要的作用,。此外,，腫瘤細胞中凝溶膠蛋白的表達量也發(fā)生變化,。凝溶膠蛋白的變異還是某些遺傳疾病的基礎。
雖然最初認為凝溶膠蛋白是一種腫瘤抑制基因,，但最新研究發(fā)現(xiàn)凝溶膠蛋白在某些腫瘤中的表達與預后差相關,。在體外，凝溶膠蛋白具有抗凋亡和遷移的功能,，并且對是某些類型腫瘤細胞的侵襲是至關重要的,。
用免疫組化檢查，科研人員發(fā)凝溶膠蛋白在侵入肝器官中的癌組織邊界中高表達,。雖然凝溶膠蛋白對細胞遷移過程中片狀偽足的形成,，誘導腫瘤的侵襲有貢獻，但目前還不清楚其中明確機制,。使用過表達技術和RNA干擾技術過表達或是敲除大腸癌細胞中凝溶膠蛋白的表達后,，研究人員考察了凝溶膠蛋白對侵襲能力的影響。
研究表明,，凝溶膠蛋白對大腸癌細胞侵入基底膜是必須的,。微陣列分析和定量PCR研究表明，凝溶膠蛋白的過度表達引起的促進大腸癌的腫瘤細胞中侵襲基因表達上調,，這其中包括降解基質的尿激酶型纖溶酶原激活劑（uPA）,。
相反，凝溶膠蛋白被抑制后,，uPA的表達水平也會降低,，uPA的分泌也受到相應的抑制。凝溶膠蛋白過度表達的腫瘤細胞用特異性的uPA或其受體抗體阻斷后侵襲能減弱,，可見uPA/及其受體uPAR對凝溶膠蛋白促進腫瘤細胞侵襲是至關重要的,。總之,，研究數據證實凝溶膠蛋白通過調節(jié)uPA/uPAR信號級聯(lián)促進大腸癌腫瘤細胞的侵襲,。相關研究論文發(fā)表在PLoS One雜志上。（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.
