Possible regulation of the immune modulator tetraspanin CD81 by alpha-synuclein in melanoma

We probed the mechanism by which the Parkinsons disease-associated protein α–synuclein (α–syn)/ SNCA promotes the pathogenesis and progression of melanoma. We found that the human melanoma cell line SK–MEL–28 in which SNCA is knocked out ( SNCA -KO) has low levels of tetraspanin CD81, which is a cell-surface protein that promotes invasion, migration, and immune suppression. Analyzing data from the Cancer Genome Atlas, we show that SNCA and CD81 mRNA levels are positively correlated in melanoma; melanoma survival is inversely related to the levels of SNCA and CD81 ; and SNCA / CD81 are inversely related to the expression of key cytokine genes ( IL12A , IL12B , IFN , IFNG , PRF1 and GZMB ) for immune activation and immune cell-mediated killing of melanoma cells. We propose that high levels of α–syn and CD81 in melanoma and in immune cells drive invasion and migration and in parallel cause an immunosuppressive microenvironment; these contributing factors lead to aggressive melanomas.