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Gewählte Publikation:

Kinslechner, K; Schütz, B; Pistek, M; Rapolter, P; Weitzenböck, HP; Hundsberger, H; Mikulits, W; Grillari, J; Röhrl, C; Hengstschläger, M; Stangl, H; Mikula, M; .
(2019): Loss of SR-BI Down-Regulates MITF and Suppresses Extracellular Vesicle Release in Human Melanoma.
Int J Mol Sci. 2019; 20(5): FullText FullText_BOKU

Abstract:
Melanoma is a skin tumor with a high tendency for metastasis and thus is one of the deadliest cancers worldwide. Here, we investigated the expression of the scavenger receptor class B type 1 (SR-BI), a high-density lipoprotein (HDL) receptor, and tested for its role in melanoma pigmentation as well as extracellular vesicle release. We first analyzed the expression of SR-BI in patient samples and found a strong correlation with MITF expression as well as with the melanin synthesis pathway. Hence, we asked whether SR-BI could also play a role for the secretory pathway in metastatic melanoma cells. Interestingly, gain- and loss-of-function of SR-BI revealed regulation of the proto-oncogene MET. In line, SR-BI knockdown reduced expression of the small GTPase RABB22A, the ESCRT-II protein VPS25, and SNAP25, a member of the SNARE complex. Accordingly, reduced overall extracellular vesicle generation was detected upon loss of SR-BI. In summary, SR-BI expression in human melanoma enhances the formation and transport of extracellular vesicles, thereby contributing to the metastatic phenotype. Therapeutic targeting of SR-BI would not only interfere with cholesterol uptake, but also with the secretory pathway, therefore suppressing a key hallmark of the metastatic program.
Autor*innen der BOKU Wien:
Grillari Johannes
BOKU Gendermonitor:

Find related publications in this database (using NML MeSH Indexing)
Cell Line, Tumor
Down-Regulation
Extracellular Vesicles/metabolism*
Gene Expression Regulation, Neoplastic
Humans
Melanoma/genetics
Melanoma/metabolism*
Microphthalmia-Associated Transcription Factor/genetics*
Microphthalmia-Associated Transcription Factor/metabolism
Scavenger Receptors, Class B/genetics*
Scavenger Receptors, Class B/metabolism
Synaptosomal-Associated Protein 25/genetics
Synaptosomal-Associated Protein 25/metabolism
Vesicular Transport Proteins/genetics
Vesicular Transport Proteins/metabolism
rab GTP-Binding Proteins/genetics
rab GTP-Binding Proteins/metabolism

Find related publications in this database (Keywords)
SCARB1
pigmentation
secretory pathway
melanoma metastasis
cMET
extracellular vesicles


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