The role of HIF prolyl hydroxylases in tumour growth
Tumour hypoxia is a well-known microenvironmental factor that causes cancer progression and resistance to cancer treatment. This involves multiple mechanisms of which the best-understood ones are mediated through transcriptional gene activation by the hypoxia-inducible factors (HIFs). HIFs in turn a...
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| Format: | Online |
| Language: | English |
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Blackwell Publishing Ltd
2010
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823110/ |
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pubmed-3823110 |
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pubmed-38231102015-04-20 The role of HIF prolyl hydroxylases in tumour growth Jokilehto, Terhi Jaakkola, Panu M Reviews Tumour hypoxia is a well-known microenvironmental factor that causes cancer progression and resistance to cancer treatment. This involves multiple mechanisms of which the best-understood ones are mediated through transcriptional gene activation by the hypoxia-inducible factors (HIFs). HIFs in turn are regulated in response to oxygen availability by a family of iron- and 2-oxoglutarate-dependent dioxygenases, the HIF prolyl hydroxylases (PHDs). PHDs inactivate HIFs in normoxia by activating degradation of the HIF-α subunit but release HIF activation in poorly oxygenated conditions. The function of HIF in tumours is fairly well characterized but our understanding on the outcome of PHDs in tumours is much more limited. Here we review the function of PHDs on the HIF system, the expression of PHDs in human tumours as well as their putative function in cancer. The PHDs may have either tumour promoting or suppressing activity. Their outcome in cancer depends on the cell and cancer type-specific expression and on the availability of diverse natural PHD inhibitors in tumours. Moreover, besides the action of PHDs on HIF, recent data suggest PHD function in non-HIF signalling. Together the data illustrate a complex operation of the oxygen sensors in cancer. Blackwell Publishing Ltd 2010-04 2010-02-22 /pmc/articles/PMC3823110/ /pubmed/20178464 http://dx.doi.org/10.1111/j.1582-4934.2010.01030.x Text en © 2010 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Jokilehto, Terhi Jaakkola, Panu M |
| spellingShingle |
Jokilehto, Terhi Jaakkola, Panu M The role of HIF prolyl hydroxylases in tumour growth |
| author_facet |
Jokilehto, Terhi Jaakkola, Panu M |
| author_sort |
Jokilehto, Terhi |
| title |
The role of HIF prolyl hydroxylases in tumour growth |
| title_short |
The role of HIF prolyl hydroxylases in tumour growth |
| title_full |
The role of HIF prolyl hydroxylases in tumour growth |
| title_fullStr |
The role of HIF prolyl hydroxylases in tumour growth |
| title_full_unstemmed |
The role of HIF prolyl hydroxylases in tumour growth |
| title_sort |
role of hif prolyl hydroxylases in tumour growth |
| description |
Tumour hypoxia is a well-known microenvironmental factor that causes cancer progression and resistance to cancer treatment. This involves multiple mechanisms of which the best-understood ones are mediated through transcriptional gene activation by the hypoxia-inducible factors (HIFs). HIFs in turn are regulated in response to oxygen availability by a family of iron- and 2-oxoglutarate-dependent dioxygenases, the HIF prolyl hydroxylases (PHDs). PHDs inactivate HIFs in normoxia by activating degradation of the HIF-α subunit but release HIF activation in poorly oxygenated conditions. The function of HIF in tumours is fairly well characterized but our understanding on the outcome of PHDs in tumours is much more limited. Here we review the function of PHDs on the HIF system, the expression of PHDs in human tumours as well as their putative function in cancer. The PHDs may have either tumour promoting or suppressing activity. Their outcome in cancer depends on the cell and cancer type-specific expression and on the availability of diverse natural PHD inhibitors in tumours. Moreover, besides the action of PHDs on HIF, recent data suggest PHD function in non-HIF signalling. Together the data illustrate a complex operation of the oxygen sensors in cancer. |
| publisher |
Blackwell Publishing Ltd |
| publishDate |
2010 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823110/ |
| _version_ |
1612025237074870272 |