Dataset Information

Characterization of syntenin knockout exosomes from 4T1 murine breast cancer cells

ABSTRACT: Tumor cells are known to induce tumor-supporting phenotypes in surrounding stroma cells which leads to the creation of a favourable tumor niche and sustained growth as well as progression of the tumor. One mechanism how tumor cells can modulate surrounding stroma cells is through the release of extracellular vesicles. These vesicles comprise large plasma membrane-derived microvesicles (diameter 100-1000 nm) as well as the better characterized smaller exosomes (diameter <100 nm) which are derived from intraluminal vesicles inside endosomal compartments. In spite of the identification of vesicle-mediated tumor-tumor and tumor-stroma intracellular communication loops, the tumor-supporting factors present on tumor vesicles as well as the factors that regulate their export are largely unknown. One attractive candidate protein which could be involved in controlling vesicular cargo selection is the adaptor scaffolding protein syntenin/SDCBP, which is known as a marker protein highly expressed on exosomes. Syntenin is characterized by two structural protein interaction modules, the PDZ domains, which can either bind to other PDZ domains or to the C-terminus of target proteins in a sequence-specific way, thereby enabling protein-protein interactions. PDZ proteins in general are known to be involved in the recruitment and assembly of specific protein complexes, especially at the cellular plasma membrane. Syntenin is a factor that has been shown to control not only the biogenesis of exosomes, but also the sorting of specific proteins to these vesicles. While it is highly expressed in human fetal tissues, its expression is significantly downregulated in adult tissues with the exception of the heart or placenta. However, high levels of syntenin seem to be restored in advanced human cancer of different entities and thereby suggest a role for syntenin in tumor progression. Previous results from the group of Pascale Zimmermann showed that syntenin is of particular importance for regulating the sorting of its (known) target proteins to exosomes which would allow their distribution to neighboring stroma cells. To analyze which tumor-supporting factors are present on breast cancer exosomes and which of them are regulated by syntenin, exosomes from 4T1 wildtype cells (syntenin-high) and from two clones of syntenin CRISPR/Cas9 syntenin knockout cells were isolated from cell culture supernatants by differential ultracentrifugation and then analyzed and compared by label-free mass spectrometry.

INSTRUMENT(S):

ORGANISM(S): Bos Taurus (bovine) Mus Musculus (mouse)

DISEASE(S): Breast Cancer

SUBMITTER: Luc Camoin

LAB HEAD: Luc Camoin

PROVIDER: PXD007721 | Pride | 2025-08-25

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	CRISPR_msynt_1et2B.raw	Raw
	CRISPR_msynt_1et2B_160112003637.raw	Raw
	CRISPR_msynt_1et2B_EXO2.raw	Raw
	CRISPR_msynt_1et2B_EXO2_160404191420.raw	Raw
	CRISPR_msynt_3et4B.raw	Raw

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Publications

Syntenin Controls Extracellular Vesicle-Induced Tumour Migration by Regulating the Expression of Adhesion Proteins on Small Extracellular Vesicles.

Irmer Barnabas B Angenendt Allegra A Camoin Luc L Audebert Stéphane S Geyer Christiane C Gerwing Mirjam M Spiessbach Hanna H Hebel Mira M Baudelet Émilie É Wlochowitz Darius D Hansen Uwe U Bleckmann Annalen A Zimmermann Pascale P Menck Kerstin K

Journal of extracellular vesicles 20250801 8

Despite extensive proof for the tumour-supporting function of cancer-derived small extracellular vesicles (sEVs), attributions of pathological effects to specific sEV subpopulations are poorly described. In this study, we aimed to characterise a distinct sEV species under the control of Syntenin, a key regulator of endosomal sEV biogenesis, regarding its proteomic cargo and pro-tumourigenic functions. Using mass spectrometry (MS), we detected 178 down- and 236 up-regulated proteins on sEVs from ...[more]

PMID: 40831280

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