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

@article{Stein2009MACC1AN,
  title={MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis},
  author={Ulrike Stein and Wolfgang Walther and Franziska Arlt and Holger Schwabe and Janice L Smith and Iduna Dr Fichtner and Walter Birchmeier and Peter M. Schlag},
  journal={Nature Medicine},
  year={2009},
  volume={15},
  pages={59-67}
}
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… 
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TLDR
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TLDR
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TLDR
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Differential role of MACC 1 expression and its regulation of the HGF / c ‐ Met pathway between breast and colorectal cancer
TLDR
The association of MACC1 mRNA and protein expression with breast cancer survival using Cox proportional hazard models and in vitro studies provide some novel insights into the role ofMACC1, indicating that it plays different roles in breast and several other cancers.
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References

SHOWING 1-10 OF 59 REFERENCES
Experimental and clinicopathologic studies on the function of the HGF receptor in human colon cancer metastasis
TLDR
The clinicopathological data and experimental findings further support the notion that the c-met expression in human colon cancer can be considered as a marker of the metastatic potential due to its involvement in the generation of the motility signal.
Overexpression and amplification of the met/HGF receptor gene during the progression of colorectal cancer.
TLDR
Overexpression of the c-met oncogene contributes a selective growth advantage to neoplastic colorectal cells at any stage of tumor progression and amplification appears to give a further selective advantage for the acquisition of metastatic potential.
Targeting the c-Met signaling pathway in cancer.
  • B. PeruzziD. Bottaro
  • Biology, Chemistry
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 2006
TLDR
The present understanding of c-Met oncogenic signaling supports at least three avenues of pathway selective anticancer drug development: antagonism of ligand/receptor interaction, inhibition of TK catalytic activity, and blockade of intracellular receptor/effector interactions.
c-Met and hepatocyte growth factor: Potential as novel targets in cancer therapy
TLDR
Targeting of the HGF/Met pathway, alone or in combination with standard therapies, is likely to improve current therapies in Met-dependent malignancies.
Wnt signaling regulates expression of the receptor tyrosine kinase met in colorectal cancer.
TLDR
The results indicate that Met expression is part of a genetic program controlled by the Wnt pathway and suggest a role for Met in controlling the turnover and differentiation of intestinal epithelium.
The metastasis-associated gene S100A4 is a novel target of beta-catenin/T-cell factor signaling in colon cancer.
TLDR
S100A4 is a direct beta-catenin/TCF target, induces migration and invasion in vitro and metastasis in vivo, and has value for prognosis of metastasis formation in colon cancer patients.
c-MET expression level in primary colon cancer: a predictor of tumor invasion and lymph node metastases.
  • H. TakeuchiA. Bilchik D. Hoon
  • Medicine, Biology
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 2003
TLDR
This study indicates c-MET mRNA overexpression in primary CRC may be an important prognostic marker for early stage invasion and regional disease metastasis.
Activation of the Met Receptor by Cell Attachment Induces and Sustains Hepatocellular Carcinomas in Transgenic Mice
TLDR
It is shown that overexpression of the Met RTK allows activation of the receptor by cell attachment and that this form of activation can be tumorigenic, providing evidence that Met may play a role in both the genesis and maintenance of HCC, and suggesting thatMet may be a beneficial therapeutic target in tumors that overexpress the receptor.
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