生物谷：结肠和直肠癌是西方国家发生率最高的癌症之一。它常常由一块息肉开始，然后转变为富有侵略性的肿瘤，并且通常会转移到肝脏。最近发表在《癌症研究》（Cancer Research）上的文章中，来自Weizmann研究所分子细胞生物学系的Avri Ben-Ze’ev教授和Nancy Gavert博士揭开了帮助癌症转移的机制。
大多数时候，肠癌开始于一种关键蛋白——beta-catenin的变化。该蛋白的一个作用是进入细胞核来激发基因表达。但在肠癌和其它癌症中，beta-catenin在细胞中过度积累，并且错误的激发基因，最终导致癌症。
令人惊讶的是，在Ben-Ze’ev小组之前的研究中，曾在肠癌细胞中发现了其中一种被激活的基因，它负责编译L1-CAM受体。该受体常存在于神经细胞中，负责神经细胞的识别和运动。而Ben-Ze’ev之前的研究发现L1-CAM只在位于肿瘤组织入侵前端的特定细胞中存在，这表示它可能在转移中起到了重要作用。
在此次研究中，科学家发现表达了L1-CAM基因的肠癌细胞能扩散到肝脏，而那些缺乏L1-CAM的则不能。
通过和复杂系统物理系的Eytan Domany教授以及研究生Michael Sheffer合作，Ben-Ze’ev比较了经过L1-CAM诱导基因表达的培养肠癌细胞和从肠癌病人体内获得的170份组织样本，以及40份健康肠组织。在被L1-CAM诱导的160个基因中，大约有60个只在癌症组织中高度表达。Ben-Ze’ev计划进一步研究这些基因的作用，以揭开L1-CAM在转移过程中充当的角色。 （教育部科技发展中心）
原文链接：http://www.physorg.com/news107492543.html
参考文献一：
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: danijela.vignjevic@curie.fr .
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]
