ArticleCell death discovery2021
SYT8 promotes pancreatic cancer progression via the TNNI2/ERRα/SIRT1 signaling pathway.
Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Article
- SYT8 as a potential prognostic biomarker and therapeutic predictor in colorectal cancer: insights from multi-cohort transcriptomic analyses.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Review
- Understanding the Molecular Mechanisms of Incomptine A in Treating Non-Hodgkin Lymphoma Associated with U-937 Cells: Bioinformatics Approaches, Part I.Pharmaceuticals (Basel, Switzerland) · 2024Article
- SIRT1 Inhibition-Induced Mitochondrial Damage Promotes GSDME-Dependent Pyroptosis in Hepatocellular Carcinoma Cells.Molecular biotechnology · 2024Article
- A Comparison of Tools That Identify Tumor Cells by Inferring Copy Number Variations from Single-Cell Experiments in Pancreatic Ductal Adenocarcinoma.Biomedicines · 2024Article
- Fasting-induced RNF152 resensitizes gallbladder cancer cells to gemcitabine by inhibiting mTORC1-mediated glycolysis.iScience · 2024Article
- Optimization of a mouse model of pancreatic cancer to simulate the human phenotypes of metastasis and cachexia.BMC cancer · 2024Article
- Article
- Spatial transcriptomics reveals the heterogeneity and FGG+CRP+ inflammatory cancer-associated fibroblasts replace islets in pancreatic ductal adenocarcinoma.Frontiers in oncology · 2023Article
- Article
- A two-stage genome-wide association study to identify novel genetic loci associated with acute radiotherapy toxicity in nasopharyngeal carcinoma.Molecular cancer · 2022Article
- Potential roles of synaptotagmin family members in cancers: Recent advances and prospects.Frontiers in medicine · 2022Review
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Authors and funding
7 authors.
Funding
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Abstract
Pancreatic cancer is a highly lethal malignancy due to failures of early detection and high metastasis in patients. While certain genetic mutations in tumors are associated with severity, the molecular mechanisms responsible for cancer progression are still poorly understood. Synaptotagmin-8 (SYT8) is a membrane protein that regulates hormone secretion and neurotransmission, and its expression is positively regulated by the promoter of the insulin gene in pancreatic islet cells. In this study, we identified a previously unknown role of SYT8 in altering tumor characteristics in pancreatic cancer. SYT8 levels were upregulated in patient tumors and contributed towards increased cell proliferation, migration, and invasion in vitro and in vivo. Increased SYT8 expression also promoted tumor metastasis in an in vivo tumor metastasis model. Furthermore, we showed that SYT8-mediated increase in tumorigenicity was regulated by SIRT1, a protein deacetylase previously known to alter cell metabolism in pancreatic lesions. SIRT1 expression was altered by orphan nuclear receptor ERRα and troponin-1 (TNNI2), resulting in cell proliferation and migration in an SYT8-dependent manner. Together, we identified SYT8 to be a central regulator of tumor progression involving signaling via the SIRT1, ERRα, and TNNI2 axis. This knowledge may provide the basis for the development of therapeutic strategies to restrict tumor metastasis in pancreatic cancer.
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Registered trials
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