Hypoxia, Gene Expression, and Metastasis

  • Olga V. Razorenova
  • Amato J. Giaccia
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Metastasis is the primary cause of death from cancer due to the spread of disease throughout the body. Increasing evidence suggests that the hypoxic microenvironment serves as a driving force for the metastatic process. Fifty to sixty percent of solid tumors contain hypoxic areas, where the gene expression is reprogrammed by low oxygen microenvironment leading to aggressive invasive cancer cell behavior. Hypoxia upregulates multiple genes involved in different steps of metastatic process, including angiogenesis, proliferation, migration, invasion, motility, adhesion, ECM remodeling, and survival. Moreover, hypoxia confers tumor cells with chemo- and radio-resistance. At the end of this chapter, we discuss the facts linking hypoxia and cancer stem cells (CSC) mainly through the ability of hypoxic microenvironment to shift cells toward the undifferentiated phenotype.


Cancer Stem Cell Focal Adhesion Kinase Invasive Lobular Carcinoma Metastatic Process Twist Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



protein kinase B


arylhydrocarbon receptor nuclear ­translocator


clear cell renal cell carcinoma


central nervous system


cancer stem cell


epithelial–mesenchymal transition


focal adhesion kinase


factor inhibiting HIF


glioma stem cell


hypoxia-inducible factor


hypoxia-responsive element


isocitrate dehydrogenase 1


induced pluripotent stem cell




loss of heterozygosity


lysyl oxidase


mitogen-activated protein kinase


neural stem cell

PHDs 1–3

prolyl-4-hydroxylases 1–3


phosphoinositide 3 kinase


von Hippel–Lindau protein


von Hippel–Lindau gene




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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Division of Radiation and Cancer BiologyStanford UniversityStanfordUSA

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