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Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells

Bourseau-Guilmain, Erika LU ; Menard, Julien LU ; Lindqvist, E. LU ; Indira Chandran, Vineesh LU ; CHRISTIANSON, HELENA LU ; Cerezo Magaña, M.; Lidfeldt, Jon LU ; Marko-Varga, György LU ; Welinder, Charlotte LU and Belting, Mattias LU (2016) In Nature Communications 7. p.1-13
Abstract

Hypoxia promotes tumour aggressiveness and resistance of cancers to oncological treatment. The identification of cancer cell internalizing antigens for drug targeting to the hypoxic tumour niche remains a challenge of high clinical relevance. Here we show that hypoxia down-regulates the surface proteome at the global level and, more specifically, membrane proteome internalization. We find that hypoxic down-regulation of constitutive endocytosis is HIF-independent, and involves caveolin-1-mediated inhibition of dynamin-dependent, membrane raft endocytosis. Caveolin-1 overexpression inhibits protein internalization, suggesting a general negative regulatory role of caveolin-1 in endocytosis. In contrast to this global inhibitory effect, we... (More)

Hypoxia promotes tumour aggressiveness and resistance of cancers to oncological treatment. The identification of cancer cell internalizing antigens for drug targeting to the hypoxic tumour niche remains a challenge of high clinical relevance. Here we show that hypoxia down-regulates the surface proteome at the global level and, more specifically, membrane proteome internalization. We find that hypoxic down-regulation of constitutive endocytosis is HIF-independent, and involves caveolin-1-mediated inhibition of dynamin-dependent, membrane raft endocytosis. Caveolin-1 overexpression inhibits protein internalization, suggesting a general negative regulatory role of caveolin-1 in endocytosis. In contrast to this global inhibitory effect, we identify several proteins that can override caveolin-1 negative regulation, exhibiting increased internalization at hypoxia. We demonstrate antibody-mediated cytotoxin delivery and killing specifically of hypoxic cells through one of these proteins, carbonic anhydrase IX. Our data reveal that caveolin-1 modulates cell-surface proteome turnover at hypoxia with potential implications for specific targeting of the hypoxic tumour microenvironment.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Hypoxia , cancer cells
in
Nature Communications
volume
7
pages
13 pages
publisher
Nature Publishing Group
external identifiers
  • Scopus:84964863959
ISSN
2041-1723
DOI
10.1038/ncomms11371
language
English
LU publication?
yes
id
fae9928f-5caa-467f-be10-0474f0aef95f
date added to LUP
2016-06-16 08:34:00
date last changed
2016-11-28 11:55:38
@misc{fae9928f-5caa-467f-be10-0474f0aef95f,
  abstract     = {<p>Hypoxia promotes tumour aggressiveness and resistance of cancers to oncological treatment. The identification of cancer cell internalizing antigens for drug targeting to the hypoxic tumour niche remains a challenge of high clinical relevance. Here we show that hypoxia down-regulates the surface proteome at the global level and, more specifically, membrane proteome internalization. We find that hypoxic down-regulation of constitutive endocytosis is HIF-independent, and involves caveolin-1-mediated inhibition of dynamin-dependent, membrane raft endocytosis. Caveolin-1 overexpression inhibits protein internalization, suggesting a general negative regulatory role of caveolin-1 in endocytosis. In contrast to this global inhibitory effect, we identify several proteins that can override caveolin-1 negative regulation, exhibiting increased internalization at hypoxia. We demonstrate antibody-mediated cytotoxin delivery and killing specifically of hypoxic cells through one of these proteins, carbonic anhydrase IX. Our data reveal that caveolin-1 modulates cell-surface proteome turnover at hypoxia with potential implications for specific targeting of the hypoxic tumour microenvironment.</p>},
  author       = {Bourseau-Guilmain, Erika and Menard, Julien and Lindqvist, E. and Indira Chandran, Vineesh and CHRISTIANSON, HELENA and Cerezo Magaña, M. and Lidfeldt, Jon and Marko-Varga, György and Welinder, Charlotte and Belting, Mattias},
  issn         = {2041-1723},
  keyword      = {Hypoxia ,cancer cells},
  language     = {eng},
  month        = {04},
  pages        = {1--13},
  publisher    = {ARRAY(0x11b43d70)},
  series       = {Nature Communications},
  title        = {Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells},
  url          = {http://dx.doi.org/10.1038/ncomms11371},
  volume       = {7},
  year         = {2016},
}