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

Primary 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... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America 2011, Vol.108(39), pp.16369-16374
Main Author: Wong , Carmen Chak-Lui
Other Authors: Gilkes , Daniele M. , Zhang , Huafeng , Chen , Jasper , Wei , Hong , Chaturvedi , Pallavi , Fraley , Stephanie I. , Wong , Chun-Ming , Khoo , Ui-Soon , Ng , Irene Oi-Lin , Wirtz , Denis , Semenza , Gregg L.
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: National Academy of Sciences
Created: 2011
ID: ISSN: 0027-8424
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recordid: faoagrisUS201400080999
title: Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation
format: Article
creator:
  • Wong , Carmen Chak-Lui
  • Gilkes , Daniele M.
  • Zhang , Huafeng
  • Chen , Jasper
  • Wei , Hong
  • Chaturvedi , Pallavi
  • Fraley , Stephanie I.
  • Wong , Chun-Ming
  • Khoo , Ui-Soon
  • Ng , Irene Oi-Lin
  • Wirtz , Denis
  • Semenza , Gregg L.
subjects:
  • Mice
  • Collagen
  • Metastasis
  • Lungs
  • Crosslinking
  • Recruitment
  • Humans
  • Breast Neoplasms
ispartof: Proceedings of the National Academy of Sciences of the United States of America, 2011, Vol.108(39), pp.16369-16374
description: Primary 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. ; p. 16369-16374.
language: eng
source:
identifier: ISSN: 0027-8424
fulltext: fulltext
issn:
  • 00278424
  • 0027-8424
url: Link


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titleHypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation
creatorWong , Carmen Chak-Lui ; Gilkes , Daniele M. ; Zhang , Huafeng ; Chen , Jasper ; Wei , Hong ; Chaturvedi , Pallavi ; Fraley , Stephanie I. ; Wong , Chun-Ming ; Khoo , Ui-Soon ; Ng , Irene Oi-Lin ; Wirtz , Denis ; Semenza , Gregg L.
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ispartofProceedings of the National Academy of Sciences of the United States of America, 2011, Vol.108(39), pp.16369-16374
identifierISSN: 0027-8424
subjectMice ; Collagen ; Metastasis ; Lungs ; Crosslinking ; Recruitment ; Humans ; Breast Neoplasms
descriptionPrimary 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. ; p. 16369-16374.
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titleHypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation
descriptionPrimary 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. ; p. 16369-16374.
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authorWong , Carmen Chak-Lui ; Gilkes , Daniele M. ; Zhang , Huafeng ; Chen , Jasper ; Wei , Hong ; Chaturvedi , Pallavi ; Fraley , Stephanie I. ; Wong , Chun-Ming ; Khoo , Ui-Soon ; Ng , Irene Oi-Lin ; Wirtz , Denis ; Semenza , Gregg L.
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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.
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