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

Research output: Contribution to journalArticle


title = "Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells",
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 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.",
keywords = "Hypoxia , cancer cells",
author = "Erika Bourseau-Guilmain and Julien Menard and E. Lindqvist and {Indira Chandran}, Vineesh and HELENA CHRISTIANSON and {Cerezo Magana}, Myriam and Jon Lidfeldt and Gy{\"o}rgy Marko-Varga and Charlotte Welinder and Mattias Belting",
year = "2016",
month = "4",
day = "20",
doi = "10.1038/ncomms11371",
language = "English",
volume = "7",
pages = "1--13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",