Underlying Mechanisms for Distant Metastasis - Molecular Biology

BACKGROUND: 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. METHODS: This review provides an overview of the general concepts of metastasis, focusing on the most important genes and pathways involved and on interventional strategies. RESULTS: 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. CONCLUSION: 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.