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Hypoxia, Gene Expression, and Metastasis

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

Abstract

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.

Keywords

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.

Abbreviations

AKT

protein kinase B

ARNT

arylhydrocarbon receptor nuclear ­translocator

CC-RCC

clear cell renal cell carcinoma

CNS

central nervous system

CSC

cancer stem cell

EMT

epithelial–mesenchymal transition

FAK

focal adhesion kinase

FIH

factor inhibiting HIF

GSC

glioma stem cell

HIF

hypoxia-inducible factor

HRE

hypoxia-responsive element

IDH1

isocitrate dehydrogenase 1

iPS

induced pluripotent stem cell

α-KG

α-ketoglutarate

LOH

loss of heterozygosity

LOX

lysyl oxidase

MAPK

mitogen-activated protein kinase

NSC

neural stem cell

PHDs 1–3

prolyl-4-hydroxylases 1–3

PI-3K

phosphoinositide 3 kinase

pVHL

von Hippel–Lindau protein

VHL

von Hippel–Lindau gene

WT

wild-type

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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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