HIF-1-dependent Expression of Angiopoietin-like 4 and L1CAM Mediates Vascular Metastasis of Hypoxic Breast Cancer Cells to the Lungs

Most cases of breast cancer mortality are due to vascular metastasis. Breast cancer cells must intravasate through endothelial cells (ECs) to enter a blood vessel in the primary tumor and then adhere to ECs and extravasate at the metastatic site. In this study we demonstrate that inhibition of hypox...

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Autores principales: Zhang, H, Wong, CCL, Wei, H, Gilkes, DM, Korangath, P, Chaturvedi, P, Schito, L, Chen, J, Krishnamachary, B, Winnard, PT, Raman, V, Zhen, L, Mitzner, WA, Sukumar, S, Semenza, GL
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223555/
https://www.ncbi.nlm.nih.gov/pubmed/21860410
http://dx.doi.org/10.1038/onc.2011.365
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author Zhang, H
Wong, CCL
Wei, H
Gilkes, DM
Korangath, P
Chaturvedi, P
Schito, L
Chen, J
Krishnamachary, B
Winnard, PT
Raman, V
Zhen, L
Mitzner, WA
Sukumar, S
Semenza, GL
author_facet Zhang, H
Wong, CCL
Wei, H
Gilkes, DM
Korangath, P
Chaturvedi, P
Schito, L
Chen, J
Krishnamachary, B
Winnard, PT
Raman, V
Zhen, L
Mitzner, WA
Sukumar, S
Semenza, GL
author_sort Zhang, H
collection PubMed
description Most cases of breast cancer mortality are due to vascular metastasis. Breast cancer cells must intravasate through endothelial cells (ECs) to enter a blood vessel in the primary tumor and then adhere to ECs and extravasate at the metastatic site. In this study we demonstrate that inhibition of hypoxia-inducible factor activity (HIF) in breast cancer cells by RNA interference or digoxin treatment inhibits primary tumor growth and also inhibits the metastasis of breast cancer cells to the lungs by blocking the expression of angiopoietin-like 4 (ANGPTL4) and L1 cell adhesion molecule (L1CAM). ANGPTL4 is a secreted factor that inhibits EC-EC interaction, whereas L1CAM increases the adherence of breast cancer cells to ECs. Interference with HIF, ANGPTL4, or L1CAM expression inhibits vascular metastasis of breast cancer cells to the lungs.
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spelling pubmed-32235552012-10-05 HIF-1-dependent Expression of Angiopoietin-like 4 and L1CAM Mediates Vascular Metastasis of Hypoxic Breast Cancer Cells to the Lungs Zhang, H Wong, CCL Wei, H Gilkes, DM Korangath, P Chaturvedi, P Schito, L Chen, J Krishnamachary, B Winnard, PT Raman, V Zhen, L Mitzner, WA Sukumar, S Semenza, GL Oncogene Article Most cases of breast cancer mortality are due to vascular metastasis. Breast cancer cells must intravasate through endothelial cells (ECs) to enter a blood vessel in the primary tumor and then adhere to ECs and extravasate at the metastatic site. In this study we demonstrate that inhibition of hypoxia-inducible factor activity (HIF) in breast cancer cells by RNA interference or digoxin treatment inhibits primary tumor growth and also inhibits the metastasis of breast cancer cells to the lungs by blocking the expression of angiopoietin-like 4 (ANGPTL4) and L1 cell adhesion molecule (L1CAM). ANGPTL4 is a secreted factor that inhibits EC-EC interaction, whereas L1CAM increases the adherence of breast cancer cells to ECs. Interference with HIF, ANGPTL4, or L1CAM expression inhibits vascular metastasis of breast cancer cells to the lungs. 2011-08-22 2012-04-05 /pmc/articles/PMC3223555/ /pubmed/21860410 http://dx.doi.org/10.1038/onc.2011.365 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Zhang, H
Wong, CCL
Wei, H
Gilkes, DM
Korangath, P
Chaturvedi, P
Schito, L
Chen, J
Krishnamachary, B
Winnard, PT
Raman, V
Zhen, L
Mitzner, WA
Sukumar, S
Semenza, GL
HIF-1-dependent Expression of Angiopoietin-like 4 and L1CAM Mediates Vascular Metastasis of Hypoxic Breast Cancer Cells to the Lungs
title HIF-1-dependent Expression of Angiopoietin-like 4 and L1CAM Mediates Vascular Metastasis of Hypoxic Breast Cancer Cells to the Lungs
title_full HIF-1-dependent Expression of Angiopoietin-like 4 and L1CAM Mediates Vascular Metastasis of Hypoxic Breast Cancer Cells to the Lungs
title_fullStr HIF-1-dependent Expression of Angiopoietin-like 4 and L1CAM Mediates Vascular Metastasis of Hypoxic Breast Cancer Cells to the Lungs
title_full_unstemmed HIF-1-dependent Expression of Angiopoietin-like 4 and L1CAM Mediates Vascular Metastasis of Hypoxic Breast Cancer Cells to the Lungs
title_short HIF-1-dependent Expression of Angiopoietin-like 4 and L1CAM Mediates Vascular Metastasis of Hypoxic Breast Cancer Cells to the Lungs
title_sort hif-1-dependent expression of angiopoietin-like 4 and l1cam mediates vascular metastasis of hypoxic breast cancer cells to the lungs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223555/
https://www.ncbi.nlm.nih.gov/pubmed/21860410
http://dx.doi.org/10.1038/onc.2011.365
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