Interfering with aggregated α-synuclein in advanced melanoma leads to a major upregulation of MHC class II proteins.
Melanoma Res
; 34(5): 393-407, 2024 Oct 01.
Article
in En
| MEDLINE
| ID: mdl-38950202
ABSTRACT
Melanoma is the most serious and deadly form of skin cancer and with progression to advanced melanoma, the intrinsically disordered protein α-synuclein is upregulated to high levels. While toxic to dopaminergic neurons in Parkinson's disease, α-synuclein is highly beneficial for primary and metastatic melanoma cells. To gain detailed insights into this exact opposite role of α-synuclein in advanced melanoma, we performed proteomic studies of high-level α-synuclein-expressing human melanoma cell lines that were treated with the diphenyl-pyrazole small-molecule compound anle138b, which binds to and interferes with the oligomeric structure of α-synuclein. We also performed proteomic and transcriptomic studies of human melanoma xenografts that were treated systemically with the anle138b compound. The results reveal that interfering with oligomerized α-synuclein in the melanoma cells in these tumor xenografts led to a substantial upregulation and expression of major histocompatibility complex proteins, which are pertinent to enhancing anti-melanoma immune responses.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Up-Regulation
/
Alpha-Synuclein
/
Melanoma
Limits:
Animals
/
Humans
Language:
En
Journal:
Melanoma Res
Journal subject:
NEOPLASIAS
Year:
2024
Document type:
Article