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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
Wong, CCLGilkes, DMZhang, HChen, JWei, HChaturvedi, PFraley, SIWong, CMKhoo, USNg, IOLWirtz, DSemenza, GL
KeywordsExtracellular matrix
Lung metastasis
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?
DOI: http://dx.doi.org/10.1073/pnas.1113483108
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
0027-8424
2021 Impact Factor: 12.779
2020 SCImago Journal Rankings: 5.011
PubMed Central ID
PMC3182724
ISI Accession Number ID
WOS:000295255300050
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
References in Scopus

 

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.subjectExtracellular matrix-
dc.subjectLung metastasis-
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
dc.identifier.issnl0027-8424-

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