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The p75 neurotrophin receptor enhances HIF-dependent signaling in glioma

Tong, Bei LU ; Pantazopoulou, Vasiliki LU orcid ; Johansson, Elinn LU and Pietras, Alexander LU (2018) In Experimental Cell Research 371(1). p.122-129
Abstract

Tumor hypoxia is associated with several features of aggressive glioma growth, including migration, invasion, and stemness. Most of the cellular adaptation to hypoxia is mediated by the hypoxia-inducible factors HIF-1α and HIF-2α, but regulation of these factors by both oxygen-dependent and –independent mechanisms in brain tumors is only partially understood. Here, we show that the p75 neurotrophin receptor (p75NTR) is stabilized at hypoxia in murine glioma in vivo, as well as in primary human glioma cultures in vitro. Expression of p75NTR resulted in increased stabilization of HIF-1α and HIF-2α, and RNAi or pharmacologic targeting of p75NTR diminished HIF stabilization and HIF-dependent signaling at... (More)

Tumor hypoxia is associated with several features of aggressive glioma growth, including migration, invasion, and stemness. Most of the cellular adaptation to hypoxia is mediated by the hypoxia-inducible factors HIF-1α and HIF-2α, but regulation of these factors by both oxygen-dependent and –independent mechanisms in brain tumors is only partially understood. Here, we show that the p75 neurotrophin receptor (p75NTR) is stabilized at hypoxia in murine glioma in vivo, as well as in primary human glioma cultures in vitro. Expression of p75NTR resulted in increased stabilization of HIF-1α and HIF-2α, and RNAi or pharmacologic targeting of p75NTR diminished HIF stabilization and HIF-dependent signaling at hypoxia. Consequentially, p75NTR inhibition resulted in decreased migration, invasion, and stemness in response to hypoxia, suggesting that p75NTR is a central regulator of hypoxia-induced glioma aggressiveness. Together, our findings support the literature that identifies p75NTR as a potential therapeutic target in brain tumors.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Glioblastoma multiforme, HIF-1α, HIF-2α, Hypoxia, P75 neurotrophin receptor, Stemness
in
Experimental Cell Research
volume
371
issue
1
pages
8 pages
publisher
Academic Press
external identifiers
  • pmid:30092219
  • scopus:85051059075
ISSN
0014-4827
DOI
10.1016/j.yexcr.2018.08.002
language
English
LU publication?
yes
id
864cc259-d1cc-4da3-89ad-b1be0f4c3c98
date added to LUP
2018-09-12 14:05:46
date last changed
2024-10-15 07:00:50
@article{864cc259-d1cc-4da3-89ad-b1be0f4c3c98,
  abstract     = {{<p>Tumor hypoxia is associated with several features of aggressive glioma growth, including migration, invasion, and stemness. Most of the cellular adaptation to hypoxia is mediated by the hypoxia-inducible factors HIF-1α and HIF-2α, but regulation of these factors by both oxygen-dependent and –independent mechanisms in brain tumors is only partially understood. Here, we show that the p75 neurotrophin receptor (p75<sup>NTR</sup>) is stabilized at hypoxia in murine glioma in vivo, as well as in primary human glioma cultures in vitro. Expression of p75<sup>NTR</sup> resulted in increased stabilization of HIF-1α and HIF-2α, and RNAi or pharmacologic targeting of p75<sup>NTR</sup> diminished HIF stabilization and HIF-dependent signaling at hypoxia. Consequentially, p75<sup>NTR</sup> inhibition resulted in decreased migration, invasion, and stemness in response to hypoxia, suggesting that p75<sup>NTR</sup> is a central regulator of hypoxia-induced glioma aggressiveness. Together, our findings support the literature that identifies p75<sup>NTR</sup> as a potential therapeutic target in brain tumors.</p>}},
  author       = {{Tong, Bei and Pantazopoulou, Vasiliki and Johansson, Elinn and Pietras, Alexander}},
  issn         = {{0014-4827}},
  keywords     = {{Glioblastoma multiforme; HIF-1α; HIF-2α; Hypoxia; P75 neurotrophin receptor; Stemness}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{1}},
  pages        = {{122--129}},
  publisher    = {{Academic Press}},
  series       = {{Experimental Cell Research}},
  title        = {{The p75 neurotrophin receptor enhances HIF-dependent signaling in glioma}},
  url          = {{http://dx.doi.org/10.1016/j.yexcr.2018.08.002}},
  doi          = {{10.1016/j.yexcr.2018.08.002}},
  volume       = {{371}},
  year         = {{2018}},
}