TY - JOUR
T1 - Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation
AU - Wong, Carmen Chak Lui
AU - Gilkes, Daniele M.
AU - Zhang, Huafeng
AU - Chen, Jasper
AU - Wei, Hong
AU - Chaturvedi, Pallavi
AU - Fraley, Stephanie I.
AU - Wong, Chun Ming
AU - Khoo, Ui Soon
AU - Ng, Irene Oi Lin
AU - Wirtz, Denis
AU - Semenza, Gregg L.
PY - 2011/9/27
Y1 - 2011/9/27
N2 - 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.
AB - 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.
KW - Extracellular matrix
KW - Lung metastasis
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U2 - 10.1073/pnas.1113483108
DO - 10.1073/pnas.1113483108
M3 - Article
C2 - 21911388
AN - SCOPUS:80053645045
SN - 0027-8424
VL - 108
SP - 16369
EP - 16374
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 39
ER -