期刊
FASEB JOURNAL
卷 25, 期 2, 页码 590-599出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.10-167304
关键词
PI3K-Akt; guanine-nucleotide exchange factor; cell migration; growth factor receptors; cytoskeleton; G protein; microsatellite instability
资金
- Burroughs Wellcome Fund
- American Gastroenterology Association
- U.S. National Institutes of Health (NIH) [K08-DK-074019, R01-DK-067287]
- University of California, San Diego, Digestive Diseases Research Development Center
- U.S. Public Health Service [DK-080506]
- Basque Government [BFI06.300]
- Susan G. Komen [KG080079]
- NIH [CA100768]
Metastasis accounts for the majority of cancer-related deaths. Accurate prediction of metastatic potential of tumors has been elusive, and the search for clinically useful markers continues. We previously reported that GIV/Girdin triggers tumor cell migration by virtue of a C-terminal guanine-nucleotide exchange factor motif that activates G alpha i. Here we identify GIV as a metastasis-related protein whose full-length transcript (GIV-fl) is expressed exclusively in highly invasive colon, breast, and pancreatic carcinoma cells and not in their poorly invasive counterparts. A prospective, exploratory biomarker study conducted on a cohort of 56 patients with stage II colorectal cancer revealed a significant correlation between GIV-fl expression in tumor epithelium and shortened metastasis-free survival. Survival rate for patients with GIV-fl-positive tumors is significantly reduced compared with the patients with GIV-fl-negative tumors [P<0.0001; hazard ratio=0.076; CI=0.052-0.30 (95%)]. At the 5-yr mark, survival is 100% in the GIV-fl-negative group and 62 +/- 9% (mean +/- SE; P=6X10(-5)) in the GIV-fl-positive group. Furthermore, GIV-fl expression predicts a risk of mortality independent of the microsatellite stability status, a well-established prognosticator of colorectal cancers. We conclude that GIV-fl is a novel metastasis-related protein and an independent adverse prognosticator that may serve as a useful adjunct to traditional staging strategies in colorectal carcinoma.-Garcia-Marcos, M., Jung, B. H., Ear, J., Cabrera, B., Carethers, J. M., Ghosh, P. Expression of GIV/Girdin, a metastasis-related protein, predicts patient survival in colon cancer. FASEB J. 25, 590-599 (2011). www.fasebj.org
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