Pachmayr Eva, Treese Christoph, Stein Ulrike
Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Visc Med. 2017 Mar;33(1):11-20. doi: 10.1159/000454696. Epub 2017 Feb 9.
The formation of distant metastases constitutes a complex process with a variety of different genes and pathways involved. To improve patient survival, it is necessary to understand the underlying mechanisms of metastasis to allow for targeted intervention.
This review provides an overview of the general concepts of metastasis, focusing on the most important genes and pathways involved and on interventional strategies.
Cancer cells undergo different steps to form metastasis: most prominently, local invasion, intravasation, survival in the circulation, arrest at a distant organ site and extravasation, micrometastasis formation, and metastatic colonization. In order to pass these steps, different molecular pathways are of major importance: EGF/RAS/RAF/MEK/ERK, PI3K/Akt/mTOR, HGF/Met, Wnt/β-catenin, and VEGF signaling. The HGF/Met regulator MACC1 and the Wnt signaling target S100A4 have been shown to play a major role in the metastatic process. Each gene and pathway provides an opportunity for therapeutic intervention.
Since metastasis represents a highly limiting factor in cancer therapy causing 90% of cancer deaths, it is imperative to reveal the underlying mechanisms. This is fundamental for uncovering prognostic markers and new targeted therapy options.
远处转移的形成是一个复杂的过程，涉及多种不同的基因和途径。为了提高患者生存率，有必要了解转移的潜在机制以便进行靶向干预。
本综述概述了转移的一般概念，重点关注所涉及的最重要基因和途径以及干预策略。
癌细胞经历不同步骤形成转移：最显著的是局部侵袭、血管内侵入、在循环中存活、在远处器官部位滞留和血管外渗、微转移形成以及转移灶定植。为了通过这些步骤，不同的分子途径至关重要：表皮生长因子/鼠肉瘤病毒癌基因/快速增殖纤维肉瘤/丝裂原活化蛋白激酶/细胞外信号调节激酶、磷脂酰肌醇-3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白、肝细胞生长因子/间质上皮转化因子、Wnt/β-连环蛋白和血管内皮生长因子信号传导。肝细胞生长因子/间质上皮转化因子调节因子MACC1和Wnt信号传导靶点S100A4已被证明在转移过程中起主要作用。每个基因和途径都为治疗干预提供了机会。
由于转移是癌症治疗中的一个高度限制因素，导致90%的癌症死亡，因此揭示其潜在机制势在必行。这对于发现预后标志物和新的靶向治疗选择至关重要。
