Upregulation of Parkinson's disease-associated protein alpha-synuclein suppresses tumorigenesis via interaction with mGluR5 and gamma-synuclein in liver cancer

Upregulation of Parkinson's disease-associated protein alpha-synuclein suppresses tumorigenesis via interaction with mGluR5 and gamma-synuclein in liver cancer

Numerous epidemiological studies suggest a link between Parkinson's disease (PD) and cancer, indicating that PD-associated proteins may mediate the development of cancer. Here, we investigated a potential role of PD-associated protein α-synuclein in regulating liver cancer progression in vivo a...

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Bibliographic Details
Published in:Archives of biochemistry and biophysics 2023-08, Vol.744, p.109698-109698, Article 109698
Main Authors: Yang, Hui-Min, Cheng, Yun-Zhong, Hou, Tian-Zhong, Fan, Jing-Kai, Gu, Li, Zhang, Jian-Nan, Zhang, Hong
Format: Article
Language:eng
Subjects:
alpha-Synuclein - metabolism
Animals
Autophagy - physiology
Autophagy-lysosomal pathway
Carcinogenesis
Carcinoma, Hepatocellular
Cell Transformation, Neoplastic
gamma-Synuclein - genetics
gamma-Synuclein - metabolism
Humans
Liver Neoplasms
Metabotropic glutamate receptor 5
Parkinson Disease - metabolism
Rats
Receptor, Metabotropic Glutamate 5 - genetics
Receptor, Metabotropic Glutamate 5 - metabolism
Tumorigenesis
Up-Regulation
α-synuclein
γ-synuclein
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Summary:Numerous epidemiological studies suggest a link between Parkinson's disease (PD) and cancer, indicating that PD-associated proteins may mediate the development of cancer. Here, we investigated a potential role of PD-associated protein α-synuclein in regulating liver cancer progression in vivo and in vitro. We found the negative correlation of α-synuclein with metabotropic glutamate receptor 5 (mGluR5) and γ-synuclein by analyzing the data from The Cancer Genome Atlas database, liver cancer patients and hepatoma cells with overexpressed α-synuclein. Moreover, upregulated α-synuclein suppressed the growth, migration, and invasion. α-synuclein was found to associate with mGluR5 and γ-synuclein, and the truncated N-terminal of α-synuclein was essential for the interaction. Furthermore, overexpressed α-synuclein exerted the inhibitory effect on hepatoma cells through the degradation of mGluR5 and γ-synuclein via α-synuclein-dependent autophagy-lysosomal pathway (ALP). Consistently, in vivo experiments with rotenone-induced rat model of PD also confirmed that, upregulated α-synuclein in liver cancer tissues through targeting on mGluR5/α-synuclein/γ-synuclein complex inhibited tumorigenesis involving in ALP-dependent degradation of mGluR5 and γ-synuclein. These findings give an insight into an important role of PD-associated protein α-synuclein accompanied by the complex of mGluR5/α-synuclein/γ-synuclein in distant communications between PD and liver cancer, and provide a new strategy in therapeutics for the treatment of liver cancer. [Display omitted] •Upregulation of PD-associated protein α-synuclein suppresses the growth, migration and invasion of hepatoma cells.•α-synuclein is negatively related with mGluR5 and γ-synuclein in liver cancer.•α-synuclein reduces levels of mGluR5 and γ-synuclein through α-synuclein-dependent ALP in liver cancer.•Upregulation of α-synuclein suppresses tumorigenesis via interaction with mGluR5 and γ-synuclein invivo.
ISSN:0003-9861
1096-0384