School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.
Expert Rev Mol Diagn. 2015 Jan;15(1):41-8. doi: 10.1586/14737159.2015.976557. Epub 2014 Nov 5.
Fascin-1 is a filamentous actin-binding protein that crosslinks actin microfilaments into tight, parallel bundles. These bundles are important for the extension of microspikes, filopodia and invadopodia from cell surfaces and for the functionality of these protrusions in cell migration and/or dynamic sensing of the local microenvironment. Fascin-1 is absent in normal colonic epithelium, but its upregulation in colorectal adenomas and adenocarcinomas and its correlation with an aggressive clinical course has piqued the interest of many laboratories with research interests in cancer metastasis. This report summarizes current knowledge of the molecular interactions of fascin-1 in relation to its activities and mechanisms of upregulation in colorectal carcinoma cells. The status and key questions surrounding investigations of fascin-1 as a novel, early prognostic biomarker in colorectal cancer are discussed. Ongoing pre-clinical research into new migration inhibitory and anti-metastatic compounds that alter the actin cytoskeleton, and the goal of targeting fascin-1, is also discussed.
Fascin-1 是一种丝状肌动蛋白结合蛋白,可将肌动蛋白微丝交联成紧密的平行束。这些束对于从细胞表面延伸微刺、丝状伪足和侵入伪足以及对于这些突起在细胞迁移和/或对局部微环境的动态感知中的功能非常重要。Fascin-1 在正常结肠上皮中不存在,但在结直肠腺瘤和腺癌中上调,其与侵袭性临床病程相关,引起了许多对癌症转移研究感兴趣的实验室的关注。本报告总结了目前关于 fascin-1 的分子相互作用的知识,这些相互作用与其在结直肠癌细胞中的活性和上调机制有关。讨论了 fascin-1 作为结直肠癌新型早期预后生物标志物的研究现状和关键问题。还讨论了针对 fascin-1 的新的抑制迁移和抗转移化合物的临床前研究以及靶向 fascin-1 的目标。