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

被引：437

作者：

Stein, Ulrike ^{[1
,2
]}

Walther, Wolfgang ^{[1
,2
]}

Arlt, Franziska ^{[1
,2
]}

Schwabe, Holger ^{[2
]}

Smith, Janice ^{[1
]}

Fichtner, Iduna ^{[1
]}

Birchmeier, Walter ^{[1
]}

Schlag, Peter M. ^{[2
]}

机构：

[1] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany

[2] Charite, Robert Rossle Canc Hosp, Dept Surg & Surg Oncol, D-13125 Berlin, Germany

来源：

NATURE MEDICINE | 2009年 / 15卷 / 01期

关键词：

HEPATOCYTE GROWTH-FACTOR; SMALL INTERFERING RNA; C-MET; COLORECTAL-CANCER; INVASIVE GROWTH; FACTOR RECEPTOR; EPITHELIAL-CELLS; TRANSGENIC MICE; IN-VIVO; EXPRESSION;

D O I：

10.1038/nm.1889

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：59 / 67

页数：9

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