@article{42798085edcd499998ae8122dd26cdc5,
title = "Loss of SR-BI down-regulates MITF and suppresses extracellular vesicle release in human melanoma",
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.",
keywords = "ESCRT protein, high density lipoprotein receptor, microphthalmia associated transcription factor, scavenger receptor BI, small interfering RNA, vasculotropin, MITF protein, human, Rab protein, SCARB1 protein, scavenger receptor B, SNAP25 protein, synaptosomal associated protein 25, vesicular transport protein, Vps25 protein, Article, cholesterol transport, confocal microscopy, down regulation, enzyme linked immunosorbent assay, exosome, gene knockdown, human cell, immunocytochemistry, immunofluorescence, melanogenesis, melanoma, melanoma cell line, metastatic melanoma, mRNA expression level, polyacrylamide gel electrophoresis, protein expression, proto oncogene, real time polymerase chain reaction, secretory pathway, signal transduction, skin pigmentation, ultracentrifugation, Western blotting, gene expression regulation, genetics, metabolism, tumor cell line, Cell Line, Tumor, Down-Regulation, Extracellular Vesicles, Gene Expression Regulation, Neoplastic, Humans, Melanoma, Microphthalmia-Associated Transcription Factor, rab GTP-Binding Proteins, Scavenger Receptors, Class B, Synaptosomal-Associated Protein 25, Vesicular Transport Proteins, SCARB1, Extracellular vesicles, Melanoma metastasis, Secretory pathway, cMET, Pigmentation, Scavenger Receptors, Class B/genetics, rab GTP-Binding Proteins/genetics, Cell Line, Tumor, Proto-Oncogene Mas, Microphthalmia-Associated Transcription Factor/genetics, Gene Expression Regulation, Neoplastic, Extracellular Vesicles/metabolism, Melanoma/genetics, Synaptosomal-Associated Protein 25/genetics, Vesicular Transport Proteins/genetics",
author = "K. Kinslechner and Birgit Sch{\"u}tz and M. Pistek and P. Rapolter and H.P. Weitzenb{\"o}ck and H. Hundsberger and W. Mikulits and J. Grillari and C. R{\"o}hrl and M. Hengstschl{\"a}ger and H. Stangl and M. Mikula",
note = "Funding Information: Funding: This research was funded by the Austrian Science Fund (FWF): P 25336-B13 and the NFB: LS14-007. Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2019",
month = mar,
day = "1",
doi = "10.3390/ijms20051063",
language = "English",
volume = "20",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "5",
}
