ArticleInternational journal of biological sciences2022
Gamma synuclein promotes cancer metastasis through the MKK3/6-p38MAPK cascade.
Article in International journal of biological sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Traumatic Brain Injury Modulates Synuclein-Associated Transcription, Amyloid Plaque Morphology and Cognitive Performance in APPswe/PS1dE9/Blg Mice.Biomedicines · 2026Article
- Ubiquitin-specific protease 13 promotes colorectal cancer progression by stabilizing mitogen-activated protein kinase kinase 3.Molecular biomedicine · 2025Article
- Synuclein Proteoforms: Role in Health and Disease.Molecular neurobiology · 2025Review
- Ultrafast ultrasound localization microscopy for differential diagnosis of reactive hyperplasia and metastatic cervical lymph nodes: a pilot study.Quantitative imaging in medicine and surgery · 2025Article
- Unveiling histotype-specific biomarkers in ovarian carcinoma using proteomics.Molecular therapy. Oncology · 2025Article
- Modeling the dynamics of EMT reveals genes associated with pan-cancer intermediate states and plasticity.NPJ systems biology and applications · 2025Article
- Article
- Effects of MMP2 and its inhibitor TIMP2 on DNA damage, apoptosis and senescence of human lens epithelial cells induced by oxidative stress.Journal of bioenergetics and biomembranes · 2024Article
- Association between Parkinson's Disease and Cancer: New Findings and Possible Mediators.International journal of molecular sciences · 2024Review
- Dissecting gastric cancer heterogeneity and exploring therapeutic strategies using bulk and single-cell transcriptomic analysis and experimental validation of tumor microenvironment and metabolic interplay.Frontiers in pharmacology · 2024Article
- P38 kinase in gastrointestinal cancers.Cancer gene therapy · 2023Review
- An in vitro approach to understand contribution of kidney cells to human urinary extracellular vesicles.Journal of extracellular vesicles · 2023Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gamma synuclein (SNCG) is a neuronal protein that is also aberrantly overexpressed in various types of human cancer. SNCG overexpression promotes cancer invasion and metastasis. However, the mechanisms that drive cancer metastasis upon SNCG expression remain elusive. Elucidation of the mechanisms underlying the promotion of cancer metastasis by SNCG may help discover therapeutic avenues for SNCG-overexpressed cancer. Here, we show that SNCG promotes transforming growth factor-β (TGF-β)-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation. Mechanistically, SNCG promotes p38MAPK phosphorylation by interacting with the MAPK kinase 3/6 (MKK3/6) and prevents their degradation. SNCG knockdown leads to a decrease in TGF-β-induced phosphorylation of MKK3/6; and abrogates the induction of matrix metalloproteinase (MMP)-9 expression by TGF-β and its target gene Twist1. Furthermore, p38MAPK inhibition abrogates the promotion of MMP-9 expression and cancer cell invasion by SNCG. Both p38MAPK and MMP inhibitors can suppress the promotion of cancer cell invasion by SNCG. Finally, overexpression of SNCG in liver cancer cells promotes lung metastasis, which can be suppressed by the p38MAPK inhibitor. Together, our data uncover a previously unknown role of SNCG in promoting TGF-β-MKK3/6-p38MAPK signaling. This study highlights the critical role of p38MAPK in the promotion of cancer metastasis by SNCG, and indicates that p38MAPK inhibitor may serve as a potential therapeutic for SNCG-overexpressed cancer.
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