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

Nat Med. 2009 Jan;15(1):59-67. doi: 10.1038/nm.1889. Epub 2008 Dec 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / physiology
  • Carcinoma / diagnosis*
  • Carcinoma / genetics
  • Carcinoma / pathology*
  • Cells, Cultured
  • Colonic Neoplasms / diagnosis*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology*
  • Gene Expression Regulation, Neoplastic
  • Genes, Neoplasm / physiology
  • Hepatocyte Growth Factor / genetics*
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Mice
  • Mice, Nude
  • Mice, SCID
  • Molecular Sequence Data
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics*
  • Prognosis
  • Proto-Oncogene Proteins c-met / genetics*
  • Signal Transduction / genetics

Substances

  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • MACC1 protein, mouse
  • Neoplasm Proteins
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met