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Visc Med. 2017 Mar;33(1):11-20. doi: 10.1159/000454696. Epub 2017 Feb 9.

Underlying Mechanisms for Distant Metastasis - Molecular Biology.

Pachmayr E1,2, Treese C1,2,3,4, Stein U1,2,5.

Author information

1
Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
2
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
3
Department of Gastroenterology, Infectious Diseases, Rheumatology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
4
Berlin Institute of Health (BIH), Berlin, Germany.
5
German Cancer Consortium (DKTK), Heidelberg, Germany.

Abstract

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.

KEYWORDS:

Cancer therapy; Metastasis; Molecular mechanism

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