Advanced

Hypoxia and hypoxia-inducible factors in neuroblastoma

Påhlman, Sven LU and Mohlin, Sofie LU (2017) In Cell and Tissue Research1974-01-01+01:00 p.1-7
Abstract

Hypoxia (i.e., low oxygen levels) is a known feature of aggressive tumors. Cells, including tumor cells, respond to conditions of insufficient oxygen by activating a transcriptional program mainly driven by hypoxia-inducible factors (HIF)-1 and HIF-2. Both HIF-1α and HIF-2α expression levels have been shown to correlate to patient outcome in various tumor forms and in neuroblastoma, a solid childhood tumor of the sympathetic nervous system, in particular, HIF-2α marks a subpopulation of immature neural crest-like perivascularly located cells and associates with aggressive disease and distant metastasis. It has for long been recognized that the HIF-α subunits are oxygen-dependently regulated at the post-translational level, via... (More)

Hypoxia (i.e., low oxygen levels) is a known feature of aggressive tumors. Cells, including tumor cells, respond to conditions of insufficient oxygen by activating a transcriptional program mainly driven by hypoxia-inducible factors (HIF)-1 and HIF-2. Both HIF-1α and HIF-2α expression levels have been shown to correlate to patient outcome in various tumor forms and in neuroblastoma, a solid childhood tumor of the sympathetic nervous system, in particular, HIF-2α marks a subpopulation of immature neural crest-like perivascularly located cells and associates with aggressive disease and distant metastasis. It has for long been recognized that the HIF-α subunits are oxygen-dependently regulated at the post-translational level, via ubiquitination and proteasomal degradation. Evidence of oxygen-independent mechanisms of regulation, transcriptional control of EPAS1/HIF2A and possible cytoplasmic activities of HIF-2α has also emerged during recent years. In this review, we discuss these non-conventional actions of HIF-2α, its putative role as a therapeutic target and the constraints it carries, as well as the importance of HIF-2 activity in a vascularized setting, the so-called pseudo-hypoxic state.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Cancer stem cell, Hypoxia, Hypoxia-inducible factor, Neuroblastoma, Vascularization
in
Cell and Tissue Research1974-01-01+01:00
pages
7 pages
publisher
Springer
external identifiers
  • scopus:85031409456
ISSN
0302-766X
DOI
10.1007/s00441-017-2701-1
language
English
LU publication?
yes
id
e8afff90-271f-4679-918d-1d698390a1b8
date added to LUP
2017-11-20 11:26:39
date last changed
2018-05-29 09:46:15
@article{e8afff90-271f-4679-918d-1d698390a1b8,
  abstract     = {<p>Hypoxia (i.e., low oxygen levels) is a known feature of aggressive tumors. Cells, including tumor cells, respond to conditions of insufficient oxygen by activating a transcriptional program mainly driven by hypoxia-inducible factors (HIF)-1 and HIF-2. Both HIF-1α and HIF-2α expression levels have been shown to correlate to patient outcome in various tumor forms and in neuroblastoma, a solid childhood tumor of the sympathetic nervous system, in particular, HIF-2α marks a subpopulation of immature neural crest-like perivascularly located cells and associates with aggressive disease and distant metastasis. It has for long been recognized that the HIF-α subunits are oxygen-dependently regulated at the post-translational level, via ubiquitination and proteasomal degradation. Evidence of oxygen-independent mechanisms of regulation, transcriptional control of EPAS1/HIF2A and possible cytoplasmic activities of HIF-2α has also emerged during recent years. In this review, we discuss these non-conventional actions of HIF-2α, its putative role as a therapeutic target and the constraints it carries, as well as the importance of HIF-2 activity in a vascularized setting, the so-called pseudo-hypoxic state.</p>},
  author       = {Påhlman, Sven and Mohlin, Sofie},
  issn         = {0302-766X},
  keyword      = {Cancer stem cell,Hypoxia,Hypoxia-inducible factor,Neuroblastoma,Vascularization},
  language     = {eng},
  month        = {10},
  pages        = {1--7},
  publisher    = {Springer},
  series       = {Cell and Tissue Research1974-01-01+01:00},
  title        = {Hypoxia and hypoxia-inducible factors in neuroblastoma},
  url          = {http://dx.doi.org/10.1007/s00441-017-2701-1},
  year         = {2017},
}