Hypoxic regulation of metastasis via hypoxia-inducible factors

Eelke H. Gort, Arjan J. Groot, Elsken van der Wall, Paul J. van Diest, Marc A. Vooijs

Research output: Contribution to journalArticle

Abstract

Metastases formation is a major factor in disease progression and accounts for the majority of cancer deaths. The molecular mechanisms controlling invasion, dissemination to blood or lymphatic systems and spread of tumor cells to distant organs are still poorly understood. Recent observations indicate that the metastatic phenotype may already be present during the angiogenic switch of tumors. Intratumoral hypoxia correlates with poor prognosis and enhanced metastases formation. The Hypoxia Inducible Fadors (HIFs) are key molecules in the hypoxic response and play critical roles during tumor cell expansion by regulating energy metabolism and the induction of angiogenesis. Increasing evidence implicates HIF function in metastatic cell characteristics, like epithelial to mesenchymal transition, cell detachment, invasion and tumor cell seeding. Here, we review the link between tumor cell hypoxia and the acquisition of metastatic behavior. We hypothesize that polyclonal tumor selection by hypoxia enhances metastatic capacity by transcriptional control of key regulators of metastasis. This polyclonal hypoxic gene profile potentially develops into a metastatic profile, driving metastasis formation. The hypoxic gene profile in primary tumors may therefore provide a prognostic indicator in clinical decision-making.

Original languageEnglish (US)
Pages (from-to)60-67
Number of pages8
JournalCurrent Molecular Medicine
Volume8
Issue number1
DOIs
StatePublished - Feb 2008
Externally publishedYes

Fingerprint

Tumors
Neoplasm Metastasis
Cells
Neoplasms
Genes
Lymphatic System
Epithelial-Mesenchymal Transition
Energy Metabolism
Disease Progression
Hypoxia
Blood
Phenotype
Decision making
Switches
Molecules
Tumor Hypoxia

Keywords

  • Angiogenesis
  • Cancer
  • EMT
  • HIF
  • Hypoxia
  • Metastasis
  • Polyclonality

ASJC Scopus subject areas

  • Biochemistry

Cite this

Gort, E. H., Groot, A. J., van der Wall, E., van Diest, P. J., & Vooijs, M. A. (2008). Hypoxic regulation of metastasis via hypoxia-inducible factors. Current Molecular Medicine, 8(1), 60-67. https://doi.org/10.2174/156652408783565568

Hypoxic regulation of metastasis via hypoxia-inducible factors. / Gort, Eelke H.; Groot, Arjan J.; van der Wall, Elsken; van Diest, Paul J.; Vooijs, Marc A.

In: Current Molecular Medicine, Vol. 8, No. 1, 02.2008, p. 60-67.

Research output: Contribution to journalArticle

Gort, EH, Groot, AJ, van der Wall, E, van Diest, PJ & Vooijs, MA 2008, 'Hypoxic regulation of metastasis via hypoxia-inducible factors', Current Molecular Medicine, vol. 8, no. 1, pp. 60-67. https://doi.org/10.2174/156652408783565568
Gort, Eelke H. ; Groot, Arjan J. ; van der Wall, Elsken ; van Diest, Paul J. ; Vooijs, Marc A. / Hypoxic regulation of metastasis via hypoxia-inducible factors. In: Current Molecular Medicine. 2008 ; Vol. 8, No. 1. pp. 60-67.
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