Stein Ulrike, Walther Wolfgang, Arlt Franziska, Schwabe Holger, Smith Janice, Fichtner Iduna, Birchmeier Walter, Schlag Peter M
Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, Berlin, Germany.
Nat Med. 2009 Jan;15(1):59-67. doi: 10.1038/nm.1889. Epub 2008 Dec 21.
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.
我们通过对原发性和转移性癌进行全基因组表达分析，鉴定出一个与结肠癌相关的此前未被描述的基因：结肠癌转移相关基因1（MACC1）。肿瘤标本中MACC1的表达是转移形成和无转移生存期的独立预后指标。我们发现，编码肝细胞生长因子（HGF）受体MET的基因是MACC1的转录靶点。在细胞培养中，MACC1可促进结肠癌细胞的增殖、侵袭以及HGF诱导的细胞散射，并在小鼠模型中促进肿瘤生长和转移。在表达缺乏SH3结构域或富含脯氨酸基序的MACC1突变体的细胞中，这些表型消失。对于临床实践而言，MACC1将有助于识别预后不良的结直肠癌患者，并且是干预转移形成的一个有前景的新靶点。
