生物谷：結(jié)腸和直腸癌是西方國家發(fā)生率最高的癌癥之一。它常常由一塊息肉開始,，然后轉(zhuǎn)變?yōu)楦挥星致孕缘哪[瘤,，并且通常會(huì)轉(zhuǎn)移到肝臟。最近發(fā)表在《癌癥研究》（Cancer Research）上的文章中,，來自Weizmann研究所分子細(xì)胞生物學(xué)系的Avri Ben-Ze’ev教授和Nancy Gavert博士揭開了幫助癌癥轉(zhuǎn)移的機(jī)制,。
大多數(shù)時(shí)候，腸癌開始于一種關(guān)鍵蛋白——beta-catenin的變化,。該蛋白的一個(gè)作用是進(jìn)入細(xì)胞核來激發(fā)基因表達(dá),。但在腸癌和其它癌癥中，beta-catenin在細(xì)胞中過度積累,，并且錯(cuò)誤的激發(fā)基因,，最終導(dǎo)致癌癥,。
令人驚訝的是，在Ben-Ze’ev小組之前的研究中,，曾在腸癌細(xì)胞中發(fā)現(xiàn)了其中一種被激活的基因,，它負(fù)責(zé)編譯L1-CAM受體。該受體常存在于神經(jīng)細(xì)胞中,，負(fù)責(zé)神經(jīng)細(xì)胞的識(shí)別和運(yùn)動(dòng),。而Ben-Ze’ev之前的研究發(fā)現(xiàn)L1-CAM只在位于腫瘤組織入侵前端的特定細(xì)胞中存在，這表示它可能在轉(zhuǎn)移中起到了重要作用,。
在此次研究中,，科學(xué)家發(fā)現(xiàn)表達(dá)了L1-CAM基因的腸癌細(xì)胞能擴(kuò)散到肝臟，而那些缺乏L1-CAM的則不能,。
通過和復(fù)雜系統(tǒng)物理系的Eytan Domany教授以及研究生Michael Sheffer合作,，Ben-Ze’ev比較了經(jīng)過L1-CAM誘導(dǎo)基因表達(dá)的培養(yǎng)腸癌細(xì)胞和從腸癌病人體內(nèi)獲得的170份組織樣本，以及40份健康腸組織,。在被L1-CAM誘導(dǎo)的160個(gè)基因中,，大約有60個(gè)只在癌癥組織中高度表達(dá)。Ben-Ze’ev計(jì)劃進(jìn)一步研究這些基因的作用,，以揭開L1-CAM在轉(zhuǎn)移過程中充當(dāng)?shù)慕巧?（教育部科技發(fā)展中心）
原文鏈接：http://www.physorg.com/news107492543.html
參考文獻(xiàn)一：
Cancer Research 67, 6844-6853, July 15, 2007. doi: 10.1158/0008-5472.CAN-07-0929
Fascin, a Novel Target of ß-Catenin-TCF Signaling, Is Expressed at the Invasive Front of Human Colon Cancer
Danijela Vignjevic1, Marie Schoumacher1, Nancy Gavert3, Klaus-Peter Janssen4, Gloria Jih3, Marick Laé2, Daniel Louvard1, Avri Ben-Ze'ev3 and Sylvie Robine1
1 UMR 144 Centre National de la Recherche Scientifique and 2 Department of Pathology, Institut Curie, Paris, France; 3 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel; and 4 Department of Surgery, Technical University of Munich, Munich, Germany
Requests for reprints: Danijela Vignjevic, Equipe de Morphogenèse et Signalisation Cellulaires, UMR 144 Centre National de la Recherche Scientifique/Institut Curie, 25 rue d'Ulm, 75248 Paris Cedex 05, France. Phone: 33-1-42-34-63-61; Fax: 33-1-42-34-63-77; E-mail: [email protected] .
Cancer cells become metastatic by acquiring a motile and invasive phenotype. This step requires remodeling of the actin cytoskeleton and the expression of exploratory, sensory organelles known as filopodia. Aberrant ß-catenin-TCF target gene activation plays a major role in colorectal cancer development. We identified fascin1, a key component of filopodia, as a target of ß-catenin-TCF signaling in colorectal cancer cells. Fascin1 mRNA and protein expression were increased in primary cancers in a stage-dependent manner. Fascin1 was exclusively localized at the invasive front of tumors also displaying nuclear ß-catenin. Forced expression of fascin1 in colorectal cancer cells increased their migration and invasion in cell cultures and caused cell dissemination and metastasis in vivo, whereas suppression of fascin1 expression by small interfering RNA reduces cell invasion. Although expression of fascin1 in primary tumors correlated with the presence of metastases, fascin1 was not expressed in metastases. Our studies show that fascin1 expression is tightly regulated during development of colon cancer metastases and is a novel target of ß-catenin-TCF signaling. We propose that transient up-regulation of fascin1 in colorectal cancer promotes the acquisition of migratory and invasive phenotypes that lead to metastasis. Moreover, the expression of fascin1 is down-regulated when tumor cells reach their metastatic destination where migration ceases and proliferation is enhanced. Although metastasis to vital organs is often the cause of mortality, only limited success has been attained in developing effective therapeutics against metastatic disease. We propose that genes involved in cell migration and invasion, such as fascin1, could serve as novel targets for metastasis prevention. [Cancer Res 2007;67(14):6844–53]
