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Biochem Biophys Res Commun. 2010 Jul 30;398(3):482-8. doi: 10.1016/j.bbrc.2010.06.104. Epub 2010 Jul 1.

YB-1 alters MT1-MMP trafficking and stimulates MCF-7 breast tumor invasion and metastasis.

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1
The Department of Medicine, San Francisco Department of Veterans Affairs Medical Center, University of California, The Northern California Institute for Research and Education, San Francisco, CA 94121, USA. david.lovett@va.gov

Abstract

YB-1 is a member of the cold shock domain family, with complex roles in DNA structure, gene transcription and translation. YB-1 promotes chromosomal instability, and mammary gland transgenic expression induces tumors with 100% penetrance. YB-1 is linked to poor prognosis in breast carcinoma and is a strong predictor of relapse and disease-specific survival. Survival is directly tied to the extent of local invasion and distal metastasis, processes dependent upon the activity of the membrane type I-matrix metalloproteinase, MT1-MMP. Non-invasive MCF-7 breast adenocarcinoma cells were transfected with YB-1/EGFP. YB-1 protein was detected in the invadopodia of cells with a migratory phenotype. There was increased expression of MT1-MMP protein concentrated at the leading edges of motile cells, which were highly invasive in collagen three-dimensional culture. The rates of MT1-MMP protein endocytosis and recycling to the cell surface were elevated in clones expressing higher levels of YB-1 protein. Control MCF-7 cells formed nonfatal, non-invasive, differentiated adenocarcinomas in vivo. MCF-7 cells expressing a twofold increase in YB-1 formed highly anaplastic tumors with local invasion, pulmonary metastases and high lethality. We conclude that YB-1 contributes to the development of an invasive, metastatic breast carcinoma phenotype by enhanced presentation of MT1-MMP at the sites of cellular invasion.

PMID:
20599698
PMCID:
PMC2925540
DOI:
10.1016/j.bbrc.2010.06.104
[Indexed for MEDLINE]
Free PMC Article
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