title: RETRACTED: Collagen prolyl hydroxylases are essential for breast cancer metastasis.
abstract: 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.
authors.affiliation: Vascular Program, Institute for Cell Engineering; McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Daniele M
authors.initials: DM
authors.lastname: Gilkes
authors.forename: Pallavi
authors.initials: P
authors.lastname: Chaturvedi
authors.forename: Saumendra
authors.initials: S
authors.lastname: Bajpai
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Wong
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.forename: Stephen
authors.initials: S
authors.lastname: Pitcairn
authors.forename: Maimon E
authors.initials: ME
authors.lastname: Hubbi
authors.forename: Denis
authors.initials: D
authors.lastname: Wirtz
authors.forename: Gregg L
authors.initials: GL
authors.lastname: Semenza
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: C497442:HIF1A protein, human; D062385:Hydroxybenzoates; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; C018063:ethyl protocatechuate; D003094:Collagen; C510863:P4HA1 protein, human; D011393:Procollagen-Proline Dioxygenase
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