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

Biochemical and Biophysical Research Communications, ISSN: 0006-291X, Vol: 734, Page: 150631
2024
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Article Description

We probed the mechanism by which the Parkinson's 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 CD8 1 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, TNF, 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.

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