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MACC1—the first decade of a key metastasis molecule from gene discovery to clinical translation

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Abstract

Deciphering the paths to metastasis and identifying key molecules driving this process is one important issue for understanding and treatment of cancer. Such a key driver molecule is Metastasis Associated in Colon Cancer 1 (MACC1). A decade long research on this evolutionarily conserved molecule with features of a transcription factor as well as an adapter protein for versatile protein-protein interactions has shown that it has manifold properties driving tumors to their metastatic stage. MACC1 transcriptionally regulates genes involved in epithelial-mesenchymal transition (EMT), including those which are able to directly induce metastasis like c-MET, impacts tumor cell migration and invasion, and induces metastasis in solid cancers. MACC1 has proven as a valuable biomarker for prognosis of metastasis formation linked to patient survival and gives promise to also act as a predictive marker for individualized therapies in a broad variety of cancers. This review discusses the many features of MACC1 in the context of the hallmarks of cancer and the potential of this molecule as biomarker and novel therapeutic target for restriction and prevention of metastasis.

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Funding

Work in Prof. Ulrike Stein’s lab is supported by the German Cancer Consortium (DKTK).

Author information

Author notes

  1. Harikrishnan Radhakrishnan and Wolfgang Walther contributed equally to this work.

Authors and Affiliations

  1. Experimental and Clinical Research Center, Charité—Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125, Berlin, Germany

    Harikrishnan Radhakrishnan, Wolfgang Walther, Fabian Zincke, Dennis Kobelt, Francesca Imbastari, Müge Erdem, Benedikt Kortüm, Mathias Dahlmann & Ulrike Stein

  2. German Cancer Consortium (DKTK), German Cancer Research Center, Heidelberg, Germany

    Wolfgang Walther, Fabian Zincke, Dennis Kobelt, Mathias Dahlmann & Ulrike Stein

Authors
  1. Harikrishnan Radhakrishnan
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  2. Wolfgang Walther
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  3. Fabian Zincke
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  4. Dennis Kobelt
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  5. Francesca Imbastari
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  6. Müge Erdem
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  7. Benedikt Kortüm
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  8. Mathias Dahlmann
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  9. Ulrike Stein
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Corresponding author

Correspondence to Ulrike Stein.

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Radhakrishnan, H., Walther, W., Zincke, F. et al. MACC1—the first decade of a key metastasis molecule from gene discovery to clinical translation. Cancer Metastasis Rev 37, 805–820 (2018). https://doi.org/10.1007/s10555-018-9771-8

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