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Molecular targets and pathways involved in liver metastasis of colorectal cancer

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Abstract

We here summarize the current view of molecular mechanisms involved in the dissemination process of colorectal cancer cells to the liver as deduced from preclinical models. We focus on molecular aspects of the current understanding of the biology of liver metastases formation and survival, both being crucial for identification and validation of possible therapeutic targets and review the latest findings elucidating some features of the liver as a metastatic niche. In more detail, we outline the role of proteases and of major pathways such asc-MET signaling and its modulation by factors such as MACC1 and TIMP1, as well as Notch and TGFβ signaling. The relevance of these signalling pathways during tumor-stroma interactions in this context will be addressed. In addition, the functional role and validation of targets such as PRL3, Trop-2, L1CAM, S100A4, S100P, CD133, LIPC, and APOBEC3G are summarized.

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Acknowledgments

This work was supported by Grants to A.K. from Deutsche Forschungsgemeinschaft (KR2047 1-2, KR2047 1-3, KR2047 3-1, and KR2047 4-2) and the European Union Research Framework Programme 7 (HEALTH-2007-201279/Microenvimet, and NMP-2010-263307/SaveMe).

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  1. Institut für Molekulare Immunologie und Experimentelle Onkologie, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany

    Ulrich H. Weidle & Achim Krüger

  2. Roche Innovation Center Penzberg, Im Nonnenwald 2, 82377, Penzberg, Germany

    Fabian Birzele

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  1. Ulrich H. Weidle
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  2. Fabian Birzele
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  3. Achim Krüger
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Correspondence to Achim Krüger.

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Weidle, U.H., Birzele, F. & Krüger, A. Molecular targets and pathways involved in liver metastasis of colorectal cancer. Clin Exp Metastasis 32, 623–635 (2015). https://doi.org/10.1007/s10585-015-9732-3

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  • DOI: https://doi.org/10.1007/s10585-015-9732-3

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