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Hypoxia and hypoxia-inducible factors in neuroblastoma

Påhlman, Sven LU and Mohlin, Sofie LU orcid (2018) In Cell and Tissue Research 372(2). p.269-275
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.

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author
and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cancer stem cell, Hypoxia, Hypoxia-inducible factor, Neuroblastoma, Vascularization
in
Cell and Tissue Research
volume
372
issue
2
pages
269 - 275
publisher
Springer
external identifiers
  • scopus:85031409456
  • pmid:29032465
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
2021-10-06 02:39:04
@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},
  language     = {eng},
  number       = {2},
  pages        = {269--275},
  publisher    = {Springer},
  series       = {Cell and Tissue Research},
  title        = {Hypoxia and hypoxia-inducible factors in neuroblastoma},
  url          = {http://dx.doi.org/10.1007/s00441-017-2701-1},
  doi          = {10.1007/s00441-017-2701-1},
  volume       = {372},
  year         = {2018},
}