Article abstract


Nature Medicine 15, 59 - 67 (2008)
Published online: 21 December 2008 | doi:10.1038/nm.1889

MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis

Ulrike Stein1,2, Wolfgang Walther1,2, Franziska Arlt1,2, Holger Schwabe2, Janice Smith1, Iduna Fichtner1, Walter Birchmeier1 & Peter M Schlag2


We identified a previously undescribed gene associated with colon cancer by genome-wide expression analysis in primary and metastatic carcinomas: metastasis-associated in colon cancer-1, MACC1. MACC1 expression in tumor specimens is an independent prognostic indicator of metastasis formation and metastasis-free survival. We show that the gene encoding the hepatocyte growth factor (HGF) receptor, MET, is a transcriptional target of MACC1. MACC1 promotes proliferation, invasion and HGF-induced scattering of colon cancer cells in cell culture and tumor growth and metastasis in mouse models. These phenotypes are lost in cells expressing MACC1 mutants lacking the SH3 domain or the proline-rich motif. For clinical practice, MACC1 will be useful for the identification of poor prognosis subjects with colorectal cancer and is a promising new target for intervention in metastasis formation.

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  1. Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Stras zlige 10, 13125 Berlin, Germany.
  2. Department of Surgery and Surgical Oncology, Robert-Rössle Cancer Hospital, Charité University Medicine Berlin, Lindenberger Weg 80, 13125 Berlin, Germany.

Correspondence to: Ulrike Stein1,2 e-mail: ustein@mdc-berlin.de



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