Stafford Lewis J, Vaidya Kedar S, Welch Danny R
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Int J Biochem Cell Biol. 2008;40(5):874-91. doi: 10.1016/j.biocel.2007.12.016. Epub 2008 Jan 15.
The major problem for cancer patients is metastasis of the cancer from the primary tumor to secondary sites. Metastasis is the process by which tumor cells disseminate from the primary tumor, migrate through the basement membrane, survive in the circulatory system, invade into a secondary site, and start to proliferate. In the past, research had concentrated on the biology, taking more of a global view instead of a molecular view. More recently, the focus has been determining the molecular underpinnings, looking at genes that induce or inhibit metastasis. Metastasis suppressors, by definition, inhibit metastasis at any step of the metastatic cascade without blocking primary tumor growth. The expanding list of metastasis suppressors exist with every cellular compartment and have been shown to work by regulating signaling pathways that inhibit proliferation, cell migration and growth at the secondary site. Still, the biochemical basis of their inhibition is not completely known. Here we review the known metastasis suppressors and summarize the suspected mechanisms by which they inhibit metastasis.
癌症患者面临的主要问题是癌症从原发肿瘤转移至继发部位。转移是肿瘤细胞从原发肿瘤扩散、穿过基底膜、在循环系统中存活、侵入继发部位并开始增殖的过程。过去,研究集中在生物学方面,更多地从整体角度而非分子角度进行观察。最近,重点已转向确定分子基础,研究诱导或抑制转移的基因。根据定义,转移抑制因子在转移级联反应的任何步骤中抑制转移,而不阻碍原发肿瘤的生长。转移抑制因子的种类不断增加,存在于每个细胞区室,并且已证明它们通过调节抑制继发部位增殖、细胞迁移和生长的信号通路发挥作用。然而,它们抑制转移的生化基础仍不完全清楚。在此,我们综述已知的转移抑制因子,并总结它们抑制转移的推测机制。