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Int J Mol Sci ; 20(5)2019 Mar 01.
Article in English | MEDLINE | ID: mdl-30823658

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.


Subject(s)
Extracellular Vesicles/metabolism , Melanoma/metabolism , Microphthalmia-Associated Transcription Factor/genetics , Scavenger Receptors, Class B/genetics , Cell Line, Tumor , Down-Regulation , Gene Expression Regulation, Neoplastic , Humans , Melanoma/genetics , Microphthalmia-Associated Transcription Factor/metabolism , Proto-Oncogene Mas , 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
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