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Cancer Res. 2013 Jun 1;73(11):3285-96. doi: 10.1158/0008-5472.CAN-12-3963. Epub 2013 Mar 28.

Collagen prolyl hydroxylases are essential for breast cancer metastasis.

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Vascular Program, Institute for Cell Engineering; McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University, Baltimore, Maryland, USA.


The presence of hypoxia and fibrosis within the primary tumor are two major risk factors for metastasis of human breast cancer. In this study, we demonstrate that hypoxia-inducible factor 1 activates the transcription of genes encoding collagen prolyl hydroxylases that are critical for collagen deposition by breast cancer cells. We show that expression of collagen prolyl hydroxylases promotes cancer cell alignment along collagen fibers, resulting in enhanced invasion and metastasis to lymph nodes and lungs. Finally, we establish the prognostic significance of collagen prolyl hydroxylase mRNA expression in human breast cancer biopsies and show that ethyl 3,4-dihydroxybenzoate, a prolyl hydroxylase inhibitor, decreases tumor fibrosis and metastasis in a mouse model of breast cancer.

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