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Article: Inhibitors Of Hypoxia-inducible Factor 1 Block Breast Cancer Metastatic Niche Formation And Lung Metastasis

TitleInhibitors Of Hypoxia-inducible Factor 1 Block Breast Cancer Metastatic Niche Formation And Lung Metastasis
Authors
Issue Date2012
PublisherSpringer. The Journal's web site is located at http://www.springer.com/biomed/molecular/journal/109
Citation
Journal of Molecular Medicine, 2012, v. 90 n. 7, p. 803-15 How to Cite?
AbstractIntratumoral hypoxia, a frequent finding in metastatic cancer, results in the activation of hypoxia-inducible factors (HIFs). HIFs are implicated in many steps of breast cancer metastasis, including metastatic niche formation through increased expression of lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) proteins, enzymes that remodel collagen at the metastatic site and recruit bone marrow-derived cells (BMDCs) to the metastatic niche. We investigated the effect of two chemically and mechanistically distinct HIF inhibitors, digoxin and acriflavine, on breast cancer metastatic niche formation. Both drugs blocked the hypoxia-induced expression of LOX and LOXL proteins, collagen cross-linking, CD11b(+) BMDC recruitment, and lung metastasis in an orthotopic breast cancer model. Patients with HIF-1 alpha-overexpressing breast cancers are at increased risk of metastasis and mortality and our results suggest that such patients may benefit from aggressive therapy that includes a HIF inhibitor.
Persistent Identifierhttp://hdl.handle.net/10722/186456
ISSN
2015 Impact Factor: 4.855
2015 SCImago Journal Rankings: 2.165
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWong, CCLen_US
dc.contributor.authorZhang, Hen_US
dc.contributor.authorGilkes, DMen_US
dc.contributor.authorChen, Jen_US
dc.contributor.authorWei, Hen_US
dc.contributor.authorChaturvedi, Pen_US
dc.contributor.authorHubbi, MEen_US
dc.contributor.authorSemenza, GLen_US
dc.date.accessioned2013-08-20T12:09:09Z-
dc.date.available2013-08-20T12:09:09Z-
dc.date.issued2012en_US
dc.identifier.citationJournal of Molecular Medicine, 2012, v. 90 n. 7, p. 803-15en_US
dc.identifier.issn0946-2716en_US
dc.identifier.urihttp://hdl.handle.net/10722/186456-
dc.description.abstractIntratumoral hypoxia, a frequent finding in metastatic cancer, results in the activation of hypoxia-inducible factors (HIFs). HIFs are implicated in many steps of breast cancer metastasis, including metastatic niche formation through increased expression of lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) proteins, enzymes that remodel collagen at the metastatic site and recruit bone marrow-derived cells (BMDCs) to the metastatic niche. We investigated the effect of two chemically and mechanistically distinct HIF inhibitors, digoxin and acriflavine, on breast cancer metastatic niche formation. Both drugs blocked the hypoxia-induced expression of LOX and LOXL proteins, collagen cross-linking, CD11b(+) BMDC recruitment, and lung metastasis in an orthotopic breast cancer model. Patients with HIF-1 alpha-overexpressing breast cancers are at increased risk of metastasis and mortality and our results suggest that such patients may benefit from aggressive therapy that includes a HIF inhibitor.en_US
dc.languageengen_US
dc.publisherSpringer. The Journal's web site is located at http://www.springer.com/biomed/molecular/journal/109en_US
dc.relation.ispartofJournal of Molecular Medicineen_US
dc.rightsThe original publication is available at www.springerlink.comen_US
dc.subject.meshBone Marrow Cells - drug effects - metabolism - pathologyen_US
dc.subject.meshBreast Neoplasms - genetics - metabolism - pathologyen_US
dc.subject.meshHypoxia-Inducible Factor 1 - antagonists and inhibitors - metabolismen_US
dc.subject.meshLung Neoplasms - genetics - metabolism - secondaryen_US
dc.subject.meshNeoplasm Metastasisen_US
dc.titleInhibitors Of Hypoxia-inducible Factor 1 Block Breast Cancer Metastatic Niche Formation And Lung Metastasisen_US
dc.typeArticleen_US
dc.identifier.emailWong, CCL: carmencl@pathology.hku.hken_US
dc.identifier.authorityWong, CCL=rp01602en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1007/s00109-011-0855-yen_US
dc.identifier.pmid22231744en_US
dc.identifier.pmcidPMC3437551en_US
dc.identifier.hkuros219800en_US
dc.identifier.hkuros219799-
dc.identifier.volume90en_US
dc.identifier.issue7en_US
dc.identifier.spage803en_US
dc.identifier.epage15en_US
dc.identifier.isiWOS:000305734700009-
dc.publisher.placeGermanyen_US

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