Src in endosomal membranes promotes exosome secretion and tumor progression View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Tomoya Hikita, Atsushi Kuwahara, Risayo Watanabe, Mamiko Miyata, Chitose Oneyama

ABSTRACT

c-Src is a membrane-associated tyrosine kinase that has key roles in the signaling transduction that controls cell growth, adhesion, and migration. In the early stage of carcinogenesis, c-Src is activated under the plasma membrane and transduces oncogenic signals. Here we show that c-Src localized to the endosomal membrane has unique functions in c-Src-transformed cells. Our results indicate that activated c-Src in the endosomal membrane promoted the secretion of exosomes, in which c-Src was encapsulated. In addition, the ESCRT-interacting molecule, Alix was identified as a c-Src-interacting protein in exosomes. We revealed that the interaction between the SH3 domain of c-Src and the proline-rich region of Alix activates ESCRT-mediated intra-luminal vesicle (ILV) formation, resulting in the upregulation of exosome secretion in c-Src-transformed cells. We observed also a correlation between malignant phenotypes and Alix-dependent aberrant exosome secretion in Src-upregulated cancer cells. Collectively, our findings provide a unique mechanism for the upregulation of exosomes in cancer cells, as well as new insights into the significance of exosome secretion in cancer progression. More... »

PAGES

3265

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-019-39882-z

    DOI

    http://dx.doi.org/10.1038/s41598-019-39882-z

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112466685

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30824759


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    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-39882-z'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-39882-z'

    RDF/XML is a standard XML format for linked data.

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