Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells
(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.
(Less)
- author
- Bourseau-Guilmain, Erika
LU
; Menard, Julien
LU
; Lindqvist, E.
LU
; Indira Chandran, Vineesh
LU
; CHRISTIANSON, HELENA
LU
; Cerezo Magana, Myriam
LU
; Lidfeldt, Jon LU
; Marko-Varga, György LU ; Welinder, Charlotte LU and Belting, Mattias LU
- organization
- publishing date
- 2016-04-20
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Hypoxia, cancer cells
- in
- Nature Communications
- volume
- 7
- article number
- 11371
- pages
- 13 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:84964863959
- pmid:27094744
- wos:000374566100001
- 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
- 2024-08-23 16:23:59
@article{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 Magana, Myriam and Lidfeldt, Jon and Marko-Varga, György and Welinder, Charlotte and Belting, Mattias}}, issn = {{2041-1723}}, keywords = {{Hypoxia; cancer cells}}, language = {{eng}}, month = {{04}}, pages = {{1--13}}, publisher = {{Nature Publishing Group}}, series = {{Nature Communications}}, title = {{Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells}}, url = {{http://dx.doi.org/10.1038/ncomms11371}}, doi = {{10.1038/ncomms11371}}, volume = {{7}}, year = {{2016}}, }