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

Official URL:https://doi.org/10.1038/nm.1889
PubMed:View item in PubMed
Creators Name:Stein, U. and Walther, W. and Arlt, F. and Schwabe, H. and Smith, J. and Fichtner, I. and Birchmeier, W. and Schlag, P.M.
Journal Title:Nature Medicine
Journal Abbreviation:Nat Med
Volume:15
Number:1
Page Range:59-67
Date:January 2009
Keywords:Amino Acid Sequence, Base Sequence, Carcinoma, Cultured Cells, Colonic Neoplasms, Neoplastic Gene Expression Regulation, Neoplasm Genes, Hepatocyte Growth Factor, Nude Mice, SCID Mice, Molecular Sequence Data, Neoplasm Metastasis, Prognosis, Proto-Oncogene Proteins c-met, Signal Transduction, Biological Tumor Markers, Animals, Mice
Abstract: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.
ISSN:1078-8956
Publisher:Nature Publishing Group (U.S.A.)
Item Type:Article

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