Loss of SR-BI Down-Regulates MITF and Suppresses Extracellular Vesicle Release in Human Melanoma

Autor: Kinslechner, Katharina, Schütz, Birgit, Pistek, Martina, Rapolter, Philipp, Weitzenböck, Hans P., Hundsberger, Harald, Mikulits, Wolfgang, Grillari, Johannes, Röhrl, Clemens, Hengstschläger, Markus, Stangl, Herbert, Mikula, Mario
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 20, Iss 5, p 1063 (2019)
Volume 20
Issue 5
ISSN: 1422-0067
Popis: 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.
Databáze: OpenAIRE
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