Metabolomics

Dataset Information

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ECM deposition is driven by caveolin1-dependent regulation of exosomal biogenesis and cargo sorting


ABSTRACT:

The composition and physical properties of the extracellular matrix (ECM) critically influence tumor progression, but the molecular mechanisms underlying ECM layering are poorly understood. Tumor-stroma interaction is critically dependent on cell-cell communication mediated by exosomes, small vesicles generated within multivesicular bodies (MVBs). Here, we show that caveolin-1 (Cav1) is a central modulator of both exosome biogenesis and exosomal protein cargo sorting through the regulation of cholesterol content at the endosomal compartment/MVBs. Quantitative proteomics profiling revealed that Cav1 is required for exosomal sorting of ECM protein cargo subsets including tenascin-C (TnC), and for fibroblast-derived exosomes to efficiently depose ECM and promote tumor cell invasiveness. Cav1-driven exosomal ECM deposition not only promotes local stromal remodeling, but also the generation of distant ECM-enriched stromal niches. These results support a model by which Cav1 is a central regulatory hub for tumor-stroma interactions through a novel exosome-dependent ECM deposition mechanism.


Linked studies: MTBLS1969

INSTRUMENT(S): Liquid Chromatography MS - positive - reverse phase

SUBMITTER: Alessia Ferrarini 

PROVIDER: MTBLS1977 | MetaboLights | 2020-10-07

REPOSITORIES: MetaboLights

Dataset's files

Source:
Action DRS
MTBLS1977 Other
FILES Other
a_MTBLS1977_LC-MS_positive_reverse-phase_metabolite_profiling.txt Txt
i_Investigation.txt Txt
m_MTBLS1977_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsv Tabular
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