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Exosome uptake depends on ERK1/2-heat shock protein 27 signalling and lipid raft-mediated endocytosis negatively regulated by caveolin-1.

Svensson, Katrin LU ; Christianson, Helena LU ; Wittrup, Anders LU ; Bourseau-Guilmain, Erika LU ; Lindqvist, Eva LU ; Svensson, Lena M LU ; Mörgelin, Matthias LU and Belting, Mattias LU (2013) In Journal of Biological Chemistry 288(24). p.17713-17724
Abstract
The role of exosomes in cancer can be inferred from the observation that they transfer tumor cell derived genetic material and signalling proteins, resulting in e.g. increased tumor angiogenesis and metastasis. However, the membrane transport mechanisms and the signalling events involved in the uptake of these virus-like particles remain ill-defined. We now report that internalization of exosomes derived from glioblastoma (GBM) cells involves nonclassical, lipid raft-dependent endocytosis. Importantly, we show that the lipid raft associated protein caveolin-1 (CAV1), in analogy with its previously described role in virus uptake, negatively regulates the uptake of exosomes. We find that exosomes induce the phosphorylation of several... (More)
The role of exosomes in cancer can be inferred from the observation that they transfer tumor cell derived genetic material and signalling proteins, resulting in e.g. increased tumor angiogenesis and metastasis. However, the membrane transport mechanisms and the signalling events involved in the uptake of these virus-like particles remain ill-defined. We now report that internalization of exosomes derived from glioblastoma (GBM) cells involves nonclassical, lipid raft-dependent endocytosis. Importantly, we show that the lipid raft associated protein caveolin-1 (CAV1), in analogy with its previously described role in virus uptake, negatively regulates the uptake of exosomes. We find that exosomes induce the phosphorylation of several downstream targets known to associate with lipid rafts as signalling and sorting platforms, such as extracellular signal-regulated kinase-1/2 (ERK1/2) and heat shock protein 27 (HSP27). Interestingly, exosome uptake appears dependent on unperturbed ERK1/2-HSP27 signalling, and ERK1/2 phosphorylation is under negative influence by CAV1 during internalization of exosomes. These findings significantly advance our general understanding of exosome-mediated uptake and offer potential strategies for how this pathway may be targeted through modulation of CAV1 expression and ERK1/2 signaling. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
288
issue
24
pages
17713 - 17724
publisher
ASBMB
external identifiers
  • wos:000320380600061
  • pmid:23653359
  • scopus:84879046970
ISSN
1083-351X
DOI
10.1074/jbc.M112.445403
language
English
LU publication?
yes
id
1bc316f9-da31-4bed-b5d1-6fb724bdca31 (old id 3804773)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23653359?dopt=Abstract
date added to LUP
2013-06-06 15:39:39
date last changed
2019-05-19 03:01:17
@article{1bc316f9-da31-4bed-b5d1-6fb724bdca31,
  abstract     = {The role of exosomes in cancer can be inferred from the observation that they transfer tumor cell derived genetic material and signalling proteins, resulting in e.g. increased tumor angiogenesis and metastasis. However, the membrane transport mechanisms and the signalling events involved in the uptake of these virus-like particles remain ill-defined. We now report that internalization of exosomes derived from glioblastoma (GBM) cells involves nonclassical, lipid raft-dependent endocytosis. Importantly, we show that the lipid raft associated protein caveolin-1 (CAV1), in analogy with its previously described role in virus uptake, negatively regulates the uptake of exosomes. We find that exosomes induce the phosphorylation of several downstream targets known to associate with lipid rafts as signalling and sorting platforms, such as extracellular signal-regulated kinase-1/2 (ERK1/2) and heat shock protein 27 (HSP27). Interestingly, exosome uptake appears dependent on unperturbed ERK1/2-HSP27 signalling, and ERK1/2 phosphorylation is under negative influence by CAV1 during internalization of exosomes. These findings significantly advance our general understanding of exosome-mediated uptake and offer potential strategies for how this pathway may be targeted through modulation of CAV1 expression and ERK1/2 signaling.},
  author       = {Svensson, Katrin and Christianson, Helena and Wittrup, Anders and Bourseau-Guilmain, Erika and Lindqvist, Eva and Svensson, Lena M and Mörgelin, Matthias and Belting, Mattias},
  issn         = {1083-351X},
  language     = {eng},
  number       = {24},
  pages        = {17713--17724},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Exosome uptake depends on ERK1/2-heat shock protein 27 signalling and lipid raft-mediated endocytosis negatively regulated by caveolin-1.},
  url          = {http://dx.doi.org/10.1074/jbc.M112.445403},
  volume       = {288},
  year         = {2013},
}