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MACC1 — more than metastasis? Facts and predictions about a novel gene

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Abstract

We recently identified the metastasis-associated in colon cancer 1 (MACC1) gene by a genome-wide search for differentially expressed genes in human colon cancer tissues, metastases, and normal tissues. Based on MACC1 expression in primary colon cancers, which did not present with metastases, our negative and positive prediction for metachronous metastasis was correct in 80% and 74% of cases, respectively. The 5-year-survival was 80% for MACC1 low expressors, but 15% for individuals who showed high MACC1 expression in their primary tumors. MACC1 induces migration, invasion and proliferation in cell culture, and liver and lung metastases in xenograft models. Here, we describe features of MACC1 beyond its utility as an indicator of metastasis. We elucidate its genomic localization and organization, its predicted splice variants, and single nucleotide polymorphisms. We discuss the MACC1 protein domain structure, posttranslational modifications, its conservation through evolution, and some family ties to SH3BP4. Furthermore, we summarize the predicted expressions of MACC1 in normal and malignant human tissues. We also evaluate the MACC1 levels in the context of one of its transcriptional targets, the receptor tyrosine kinase Met that activates the hepatocyte growth factor/Met signaling pathway, leading to enhanced cell motility, invasion, and metastasis.

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Acknowledgement

The authors thank Robert H. Shoemaker, National Cancer Institute-Frederick, Frederick, MD, Franziska Arlt, ECRC/Charité University Medicine Berlin, and Miguel A. Andrade-Navarro, Max-Delbrück-Center for Molecular Medicine, Berlin, for critically reading the manuscript.

Conflict of interest statement

The authors declare that they have no conflict of interests.

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Authors and Affiliations

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

    Ulrike Stein, Mathias Dahlmann & Wolfgang Walther

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  1. Ulrike Stein
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  2. Mathias Dahlmann
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Correspondence to Ulrike Stein.

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Stein, U., Dahlmann, M. & Walther, W. MACC1 — more than metastasis? Facts and predictions about a novel gene. J Mol Med 88, 11–18 (2010). https://doi.org/10.1007/s00109-009-0537-1

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