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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Tokyo Medical University
  • Skåne University Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi

Nyckelord

Originalspråkengelska
Artikelnummer11371
Sidor (från-till)1-13
Antal sidor13
TidskriftNature Communications
Volym7
StatusPublished - 2016 apr 20
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

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

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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