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Article: Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation

TitleHypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation
Authors
Issue Date2011
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2011, v. 108 n. 39, p. 16369-16374 How to Cite?
AbstractPrimary tumors facilitate metastasis by directing bone marrow-derived cells (BMDCs) to colonize the lungs before the arrival of cancer cells. Here, we demonstrate that hypoxia-inducible factor 1 (HIF-1) is a critical regulator of breast cancer metastatic niche formation through induction of multiple members of the lysyl oxidase (LOX) family, including LOX, LOX-like 2, and LOX-like 4, which catalyze collagen cross-linking in the lungs before BMDC recruitment. Only a subset of LOX family members was expressed in any individual breast cancer, but HIF-1 was required for expression in each case. Knockdown of HIF-1 or hypoxia-induced LOX family members reduced collagen cross-linking, CD11b + BMDC recruitment, and metastasis formation in the lungs of mice after orthotopic transplantation of human breast cancer cells. Metastatic niche formation is an HIF-1-dependent event during breast cancer progression.
Persistent Identifierhttp://hdl.handle.net/10722/148650
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Emerald Foundation
National Institutes of HealthU54-CA143868
T32-CA130840
Funding Information:

We thank Karen Padgett (Novus Biologicals Inc.) for providing antibodies against HIF-1 beta, HIF-2 alpha, LOXL2, LOXL4, CD11b, and IgG control and Rashmi Bankoti, Sergio Rey, and Weibo Luo for advice. This work was supported by grants from the Emerald Foundation and National Institutes of Health (Grant U54-CA143868). D. M. G. was supported by NIH Grant T32-CA130840. G. L. S. is the C. Michael Armstrong Professor at The Johns Hopkins University School of Medicine. C. C.-L. W. is a Croucher Foundation Fellow.

References

 

DC FieldValueLanguage
dc.contributor.authorWong, CCLen_US
dc.contributor.authorGilkes, DMen_US
dc.contributor.authorZhang, Hen_US
dc.contributor.authorChen, Jen_US
dc.contributor.authorWei, Hen_US
dc.contributor.authorChaturvedi, Pen_US
dc.contributor.authorFraley, SIen_US
dc.contributor.authorWong, CMen_US
dc.contributor.authorKhoo, USen_US
dc.contributor.authorNg, IOLen_US
dc.contributor.authorWirtz, Den_US
dc.contributor.authorSemenza, GLen_US
dc.date.accessioned2012-05-29T06:14:23Z-
dc.date.available2012-05-29T06:14:23Z-
dc.date.issued2011en_US
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2011, v. 108 n. 39, p. 16369-16374en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttp://hdl.handle.net/10722/148650-
dc.description.abstractPrimary tumors facilitate metastasis by directing bone marrow-derived cells (BMDCs) to colonize the lungs before the arrival of cancer cells. Here, we demonstrate that hypoxia-inducible factor 1 (HIF-1) is a critical regulator of breast cancer metastatic niche formation through induction of multiple members of the lysyl oxidase (LOX) family, including LOX, LOX-like 2, and LOX-like 4, which catalyze collagen cross-linking in the lungs before BMDC recruitment. Only a subset of LOX family members was expressed in any individual breast cancer, but HIF-1 was required for expression in each case. Knockdown of HIF-1 or hypoxia-induced LOX family members reduced collagen cross-linking, CD11b + BMDC recruitment, and metastasis formation in the lungs of mice after orthotopic transplantation of human breast cancer cells. Metastatic niche formation is an HIF-1-dependent event during breast cancer progression.en_US
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_US
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.subject.meshBreast Neoplasms - Pathologyen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCollagen - Metabolismen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Knockdown Techniquesen_US
dc.subject.meshHumansen_US
dc.subject.meshHypoxia-Inducible Factor 1 - Genetics - Physiologyen_US
dc.subject.meshNeoplasm Metastasisen_US
dc.titleHypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formationen_US
dc.typeArticleen_US
dc.identifier.emailWong, CM:jackwong@pathology.hku.hken_US
dc.identifier.emailKhoo, US:uskhoo@hkucc.hku.hken_US
dc.identifier.emailNg, IOL:iolng@hkucc.hku.hken_US
dc.identifier.authorityWong, CM=rp00231en_US
dc.identifier.authorityKhoo, US=rp00362en_US
dc.identifier.authorityNg, IOL=rp00335en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1073/pnas.1113483108en_US
dc.identifier.pmid21911388-
dc.identifier.pmcidPMC3182724-
dc.identifier.scopuseid_2-s2.0-80053645045en_US
dc.identifier.hkuros205472-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80053645045&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume108en_US
dc.identifier.issue39en_US
dc.identifier.spage16369en_US
dc.identifier.epage16374en_US
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000295255300050-
dc.publisher.placeUnited Statesen_US

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