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

Research output: Contribution to journalArticle


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.


External organisations
  • Tokyo Medical University
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology


  • Hypoxia , cancer cells
Original languageEnglish
Article number11371
Pages (from-to)1-13
Number of pages13
JournalNature Communications
Publication statusPublished - 2016 Apr 20
Publication categoryResearch

Related research output

Menard, J., 2017, Lund: Lund University, Faculty of Medicine. 110 p.

Research output: ThesisDoctoral Thesis (compilation)

View all (1)

Related projects

View all (1)