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

Autor: Aloy NM; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, USA; Feist-Weiller Cancer Center, Louisiana State University Health Shreveport, Shreveport, USA., Coughlan C; University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Graner MW; University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Witt SN; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, USA; Feist-Weiller Cancer Center, Louisiana State University Health Shreveport, Shreveport, USA. Electronic address: stephan.witt@lsuhs.edu.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Nov 19; Vol. 734, pp. 150631. Date of Electronic Publication: 2024 Aug 30.
DOI: 10.1016/j.bbrc.2024.150631
Abstrakt: 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 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.
Competing Interests: Declaration of competing interest The authors have nothing to declare.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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