Extracellular vesicles swarm the cancer microenvironment: from tumor–stroma communication to drug intervention

Wendler, Franz; Favicchio, Rosy; Simon, Thomas R.; Alifrangis, C.; Stebbing, Justin; Giamas, Georgios

doi:10.1038/onc.2016.253

Cited by 126 publications

(114 citation statements)

References 86 publications

Supporting

Mentioning

113

Contrasting

Order By: Relevance

“…High lactate production also remodels the tumour microenvironment by contributing to angiogenesis, acting as a cancer cell metabolic fuel and inducing immunosuppression434445. Apart from Warburg effect, an increased secretion of EVs, which can shuttle reciprocal signals and other molecules between transformed and stromal cells, is another phenomenon observed during tumorigenesis64647. However, few studies have explored the link between the enhanced aerobic glycolysis and active exosome secretion in tumour cells.…”

Section: Discussionmentioning

confidence: 99%

Pyruvate kinase type M2 promotes tumour cell exosome release via phosphorylating synaptosome-associated protein 23

Yao¹,

Wang²,

Jin³

et al. 2017

Nat Commun

240

198

View full text Add to dashboard Cite

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 enables the formation of the SNARE complex to allow exosomes release. Direct phosphorylation assay and mass spectrometry confirm that PKM2 phosphorylates SNAP-23 at Ser95. Ectopic expression of non-phosphorylated SNAP-23 mutant (Ser95→Ala95) significantly reduces PKM2-mediated exosomes release whereas expression of selective phosphomimetic SNAP-23 mutants (Ser95→Glu95 but not Ser20→Glu20) rescues the impaired exosomes release induced by PKM2 knockdown. Our findings reveal a non-metabolic function of PKM2, an enzyme associated with tumour cell reliance on aerobic glycolysis, in promoting tumour cell exosome release.

show abstract

Section: Discussionmentioning

confidence: 99%

Pyruvate kinase type M2 promotes tumour cell exosome release via phosphorylating synaptosome-associated protein 23

Yao¹,

Wang²,

Jin³

et al. 2017

Nat Commun

240

198

View full text Add to dashboard Cite

show abstract

“…In pathological conditions, for example, EVs take part in tumorigenesis. They may modulate cell-to-cell communication within the tumor microenvironment, play a role in drug resistance and, migrating from the tumor to distant niches, promote metastasis formation (Wendler et al, 2017). EVs were also shown to carry and spread through the brain misfolded proteins involved in several neurodegenerative diseases, such as prion, Alzheimer's, and Parkinson's disease, and amyotrophic lateral sclerosis (Quek and Hill, 2017).…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles in Renal Pathophysiology

Pomatto

Gai

Bussolati

et al. 2017

Front. Mol. Biosci.

View full text Add to dashboard Cite

Extracellular vesicles are a heterogeneous population of microparticles released by virtually all living cells which have been recently widely investigated in different biological fields. They are typically composed of two primary types (exosomes and microvesicles) and are recently commanding increasing attention as mediators of cellular signaling. Indeed, these vesicles can affect recipient cells by carrying and delivering complex cargos of biomolecules (including proteins, lipids and nucleic acids), protected from enzymatic degradation in the environment. Their importance has been demonstrated in the pathophysiology of several organs, in particular in kidney, where different cell types secrete extracellular vesicles that mediate their communication with downstream urinary tract cells. Over the past few years, evidence has been shown that vesicles participate in kidney development and normal physiology. Moreover, EVs are widely demonstrated to be implicated in cellular signaling during renal regenerative and pathological processes. Although many EV mechanisms are still poorly understood, in particular in kidney, the discovery of their role could help to shed light on renal biological processes which are so far elusive. Lastly, extracellular vesicles secreted by renal cells gather in urine, thus becoming a great resource for disease or recovery markers and a promising non-invasive diagnostic instrument for renal disease. In the present review, we discuss the most recent findings on the role of extracellular vesicles in renal physiopathology and their potential implication in diagnosis and therapy.

show abstract

“…In addition to influencing other cancer cells, tumor-derived EVs also affect the tumor stroma (11). For example, cancer cell-derived EVs exhibit Transforming Growth Factor β (TGFβ) at their surface, which activates fibroblasts (31).…”

Section: Tumor-derived Evs As Key Players In Communication With Theirmentioning

confidence: 99%

A new role for extracellular vesicles: how small vesicles can feed tumors' big appetite

Lazar

Clement

Attané

et al. 2018

Journal of Lipid Research

View full text Add to dashboard Cite

Cancer cells must adapt their metabolism in order to meet the energy requirements for cell proliferation, survival in nutrient-deprived environments and dissemination. In particular, fatty acid metabolism is emerging as a critical process for tumors. Fatty acid metabolism can be modulated through intrinsic changes in gene expression or signaling between tumor cells, but also in response to signals from the surrounding microenvironment. Among these signals, extracellular vesicles could play an important role in fatty acid metabolism remodeling. In this review, we will present the role of extracellular vesicles in tumor progression and especially in metabolic reprogramming. Particular attention will be granted to adipocytes. These cells, which are specialized in storing and releasing FAs, are able to shift tumor metabolism towards the use of fatty acids and, subsequently, increase tumor aggressiveness. Recent work demonstrates the involvement of extracellular vesicles in this metabolic symbiosis. KeywordsAdipocytes / Cancer / Fatty acid metabolism/ Fatty acid oxidation / Fatty acid synthesis Tumor microenvironment / Exosomes / Microvesicles / Obesity /

show abstract

Extracellular vesicles swarm the cancer microenvironment: from tumor–stroma communication to drug intervention

Cited by 126 publications

References 86 publications

Pyruvate kinase type M2 promotes tumour cell exosome release via phosphorylating synaptosome-associated protein 23

Pyruvate kinase type M2 promotes tumour cell exosome release via phosphorylating synaptosome-associated protein 23

Extracellular Vesicles in Renal Pathophysiology

A new role for extracellular vesicles: how small vesicles can feed tumors' big appetite

Contact Info

Product

Resources

About