2017
DOI: 10.1038/ncomms14041
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Pyruvate kinase type M2 promotes tumour cell exosome release via phosphorylating synaptosome-associated protein 23

Abstract: Tumour cells secrete exosomes that are involved in the remodelling of the tumour–stromal environment and promoting malignancy. The mechanisms governing tumour exosome release, however, remain incompletely understood. Here we show that tumour cell exosomes secretion is controlled by pyruvate kinase type M2 (PKM2), which is upregulated and phosphorylated in tumours. During exosome secretion, phosphorylated PKM2 serves as a protein kinase to phosphorylate synaptosome-associated protein 23 (SNAP-23), which in turn… Show more

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Cited by 240 publications
(217 citation statements)
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“…These results suggest that PKM2-stimulated TEVs can increase B-cell IgG production. This finding is consistent with a previous report that PKM2 may be associated with EV release under tumor conditions (38).…”
Section: Evs Secreted From Pkm2-activated T Cells Promote B-cell Igg supporting
confidence: 94%
“…These results suggest that PKM2-stimulated TEVs can increase B-cell IgG production. This finding is consistent with a previous report that PKM2 may be associated with EV release under tumor conditions (38).…”
Section: Evs Secreted From Pkm2-activated T Cells Promote B-cell Igg supporting
confidence: 94%
“…SNAP23 is reported as a heavily phosphorylated molecule at many sites . Though our results cannot rule out the involvement of Ser95 or Ser110 phosphorylation of SNAP23 in controlling exosome secretion of CSC, we further identified RAB27B controlled endosomal–exosomal pathway of CRCSCs for modulating TME and demonstrated targeting RAB27B benefited the antitumor therapy.…”
Section: Discussionmentioning
confidence: 63%
“…The release of exosomes is a multistep processes. Though several regulators including nSMase2, phosphorylated SNAP23 and RAB27A/RAB27B are involved in cancer exosome secretion, mechanism of exosome secretion in CSCs is poorly described. Here, we found RAB27B (Fig.…”
Section: Discussionmentioning
confidence: 99%
“…Following MVE formation and transport, the final step of exosome secretion is MVE fusion to the plasma membrane, resulting in ILV release as exosomes 69 . This step is mediated in some cells by Rabs and their effectors from the exocyst complex, tethering vesicles to plasma membrane and inducing SNARE-mediated secretion [107][108][109][110][111][112][148][149][150] . So far, these mechanisms have not been implicated in necroptosis but should now be studied in this context in light of the upregulation of exocyst components in necroptotic EVs.…”
Section: Discussionmentioning
confidence: 99%