title: Molecular mechanisms mediating metastasis of hypoxic breast cancer cells.
abstract: Breast cancers contain regions of intratumoral hypoxia in which reduced O(2) 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.
authors.affiliation: Vascular Program, Institute for Cell Engineering, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. gsemenza@jhmi.edu
authors.forename: Gregg L
authors.initials: GL
authors.lastname: Semenza
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015687:Cell Hypoxia; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009363:Neoplasm Proteins; D039842:Neural Cell Adhesion Molecule L1; D000099162:Endothelial PAS Domain-Containing Protein 1