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

U Stein, W Walther, F Arlt, H Schwabe, J Smith… - Nature medicine, 2009 - nature.com
U Stein, W Walther, F Arlt, H Schwabe, J Smith, I Fichtner, W Birchmeier, PM Schlag
Nature medicine, 2009nature.com
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 …
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.
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