TY - JOUR
T1 - Molecular mechanisms mediating metastasis of hypoxic breast cancer cells
AU - Semenza, Gregg L.
N1 - Funding Information:
Breast cancer research in the author's laboratory is supported by the American Cancer Society, Johns Hopkins Institute for Cell Engineering, Komen Foundation, and National Cancer Institute. G.L.S. is the C. Michael Armstrong Professor at the Johns Hopkins University School of Medicine and an American Cancer Society Research Professor.
PY - 2012/9
Y1 - 2012/9
N2 - Breast cancers contain regions of intratumoral hypoxia in which reduced O2 availability activates the hypoxia-inducible factors HIF-1 and HIF-2, which increase the transcription of genes encoding proteins that are required for many important steps in cancer progression. Recently, HIFs have been shown to play critical roles in the metastasis of breast cancer to the lungs through the transcriptional activation of genes encoding angiopoietin-like 4 and L1 cell adhesion molecule, which promote the extravasation of circulating cancer cells from the lung vasculature, and the lysyl oxidase family members LOX, LOXL2, and LOXL4, which promote invasion and metastatic niche formation. Digoxin, a drug that inhibits HIF-1 activity, blocks primary tumor growth, vascularization, invasion, and metastasis in ex vivo and in vivo assays.
AB - Breast cancers contain regions of intratumoral hypoxia in which reduced O2 availability activates the hypoxia-inducible factors HIF-1 and HIF-2, which increase the transcription of genes encoding proteins that are required for many important steps in cancer progression. Recently, HIFs have been shown to play critical roles in the metastasis of breast cancer to the lungs through the transcriptional activation of genes encoding angiopoietin-like 4 and L1 cell adhesion molecule, which promote the extravasation of circulating cancer cells from the lung vasculature, and the lysyl oxidase family members LOX, LOXL2, and LOXL4, which promote invasion and metastatic niche formation. Digoxin, a drug that inhibits HIF-1 activity, blocks primary tumor growth, vascularization, invasion, and metastasis in ex vivo and in vivo assays.
KW - Acriflavine
KW - Angiopoietin-like 4
KW - Collagen crosslinking
KW - Digoxin
KW - Extravasation
KW - HIF-1
KW - Lysyl oxidase
KW - Metastatic niche formation
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U2 - 10.1016/j.molmed.2012.08.001
DO - 10.1016/j.molmed.2012.08.001
M3 - Review article
C2 - 22921864
AN - SCOPUS:84865575592
SN - 1471-4914
VL - 18
SP - 534
EP - 543
JO - Trends in Molecular Medicine
JF - Trends in Molecular Medicine
IS - 9
ER -