ArticleScientific reports2021
Knocking out alpha-synuclein in melanoma cells dysregulates cellular iron metabolism and suppresses tumor growth.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 53 citations in OpenAlex.
- SNCA Overexpression Induces Apoptosis in Non-Small Cell Lung Cancer via Caspase-Dependent Signaling Pathways.BioMed research international · 2026Article
- Revisiting the alpha-synuclein paradox in melanoma-Parkinson's disease connection: more than a tale of two cell fates.Cellular and molecular life sciences : CMLS · 2025Review
- Peripheral SNCADiscover oncology · 2025Article
- Expanding our understanding of synucleinopathies: proteinopathy, proteinopenia, and lipidopathy.The FEBS journal · 2025Review
- Alpha-synuclein modulates the positioning of endolysosomes in melanoma cells.Human molecular genetics · 2025Article
- Exploring α-Syn's Functions Through Ablation Models: Physiological and Pathological Implications.Cellular and molecular neurobiology · 2025Review
- Alpha-synuclein regulates nucleolar DNA double-strand break repair in melanoma.Science advances · 2025Article
- Concomitant Pathologies and Their Impact on Parkinson Disease: A Narrative Overview of Current Evidence.International journal of molecular sciences · 2025Review
- Bioinformatic analysis of ferroptosis related biomarkers and potential therapeutic targets in vitiligo.Scientific reports · 2025Article
- Link between Parkinson's disease and melanoma: insights into the influence of theFrontiers in oncology · 2025Review
- Alpha-synuclein knockout impairs melanoma development and alters DNA damage repair in the TG3 mouse model in a sex-dependent manner.Frontiers in oncology · 2025Article
- Nuclear Alpha-Synuclein in Parkinson's Disease and the Malignant Transformation in Melanoma.Neurology research international · 2025Article
- Transcriptomic analysis of melanoma cells reveals an association of α-synuclein with regulation of the inflammatory response.Scientific reports · 2024Article
- Review
- Association between Parkinson's Disease and Cancer: New Findings and Possible Mediators.International journal of molecular sciences · 2024Review
- Alpha-synuclein regulates nucleolar DNA double-strand break repair in melanoma.bioRxiv : the preprint server for biology · 2024Article
- Uncovering potential diagnostic and pathophysiological roles of α-synuclein and DJ-1 in melanoma.Cancer medicine · 2024Article
- Identification and validation of five ferroptosis-related molecular signatures in keloids based on multiple transcriptome data analysis.Frontiers in molecular biosciences · 2024Article
- Quantifying the impact of immunotherapy on RNA dynamics in cancer.Journal for immunotherapy of cancer · 2023Article
- Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The protein alpha-synuclein (α-syn) is unusual because, depending on its conformation and the type of cell in which it is expressed, it is pro-death or pro-survival, triggering neurodegeneration in Parkinson's disease and enhancing cell survival of some melanomas. To probe the function of α-syn in melanoma, we used CRISPR/Cas9 to knockout SNCA, the gene that codes for α-syn, in SK-Mel-28 melanoma cells. The SNCA-knockout clones in culture exhibited a decrease in the transferrin receptor 1 (TfR1), an increase in ferritin, an increase of reactive oxygen species and proliferated slower than control cells. These SNCA-knockout clones grafted into SCID mice grew significantly slower than the SK-Mel-28 control cells that expressed α-syn. In the excised SNCA-knockout xenografts, TfR1 decreased 3.3-fold, ferritin increased 6.2-fold, the divalent metal ion transporter 1 (DMT1) increased threefold, and the iron exporter ferroportin (FPN1) decreased twofold relative to control xenografts. The excised SNCA-KO tumors exhibited significantly more ferric iron and TUNEL staining relative to the control melanoma xenografts. Collectively, depletion of α-syn in SK-Mel-28 cells dysregulates cellular iron metabolism, especially in xenografts, yielding melanoma cells that are deficient in TfR1 and FPN1, that accumulate ferric iron and ferritin, and that undergo apoptosis relative to control cells expressing α-syn.
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