Forskningsoutput per år
Forskningsoutput per år
Erika Bourseau-Guilmain, Julien Menard, E. Lindqvist, Vineesh Indira Chandran, HELENA CHRISTIANSON, Myriam Cerezo Magana, Jon Lidfeldt, György Marko-Varga, Charlotte Welinder, Mattias Belting
Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review
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.
Originalspråk | engelska |
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Artikelnummer | 11371 |
Sidor (från-till) | 1-13 |
Antal sidor | 13 |
Tidskrift | Nature Communications |
Volym | 7 |
DOI | |
Status | Published - 2016 apr. 20 |
Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)