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.
Highlights
The scavenger receptor class B type 1 (SR-BI, gene name SCARB1) has emerged as a novel tumor marker, since its expression in different types of tumor cells has been associated with progression of the disease [1]
SR-BI Expression Pattern in Melanoma Is Associated with the Pigmentation Pathway
In order to display the distribution of SR-BI expression at each location, we used data derived from the Cancer Genome Atlas (TCGA) consortium and found highest SR-BI expression in primary lesions as well as in distant metastatic sites (Figure 1A)
Summary
The scavenger receptor class B type 1 (SR-BI, gene name SCARB1) has emerged as a novel tumor marker, since its expression in different types of tumor cells has been associated with progression of the disease [1]. Melanoma represents a highly aggressive tumor entity and SR-BI plays an important role in maintaining the metastatic phenotype in this tumor [15]. This includes the process of the epithelial-to-mesenchymal transition (EMT), migration, invasion and increased cellular glycosylation. The secretory pathway is a key cellular process determining melanoma aggressiveness and has a major impact on clinical outcome. It involves membrane trafficking at the endoplasmic reticulum and Golgi as well as the sorting of proteins to the cytoplasm membrane. We investigated whether SR-BI is involved in the generation of extracellular vesicles
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
