Hypoxia and hypoxia-inducible factors in neuroblastoma
(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
- Påhlman, Sven LU and Mohlin, Sofie LU
- organization
- publishing date
- 2018
- 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
-
- pmid:29032465
- 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
- 2024-08-19 08:51:42
@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}}, keywords = {{Cancer stem cell; Hypoxia; Hypoxia-inducible factor; Neuroblastoma; Vascularization}}, 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}}, }