Journal
CANCER AND METASTASIS REVIEWS
Volume 27, Issue 1, Pages 103-118Publisher
SPRINGER
DOI: 10.1007/s10555-007-9104-9
Keywords
cancer; metastasis; osteopontin; integrin; matrix-metalloproteinase
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Funding
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI044629] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R21DK070642] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM065113] Funding Source: NIH RePORTER
- NIAID NIH HHS [R01 AI44629] Funding Source: Medline
- NIDDK NIH HHS [R21 DK070642] Funding Source: Medline
- NIGMS NIH HHS [R01 GM65113] Funding Source: Medline
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Osteopontin is a secreted phosphoprotein that has been implicated as an important mediator of tumor metastasis and has been investigated for use as a biomarker for advanced disease and as a potential therapeutic target in the regulation of cancer metastasis. The OPN DNA sequence is highly conserved and the protein contains several important functional domains including alpha(v)beta integrin and CD44 binding sites. High levels of OPN expression correlate with tumor invasion, progression or metastasis in multiple cancer. Studies demonstrate that osteopontin mediates the molecular mechanisms which determine metastatic spread, such as prevention of apoptosis, extracellular matrix proteolysis and remodeling, cell migration, evasion of host-immune cells and neovascularization. Transcriptional regulation of OPN is complex and involves multiple pathways, including AP-1, Myc, v-Src, Runx/CBF, TGF-B/BMPs/Smad/Hox, and Wnt/beta-cocatenin/APC/GSK-3 beta/Tcf-4. The current state of knowledge of OPN biology suggests that it is an attractive target for therapeutic modulation of metastatic disease.
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