ArticleJournal of experimental & clinical cancer research : CR2022
Synaptotagmin 11 scaffolds MKK7-JNK signaling process to promote stem-like molecular subtype gastric cancer oncogenesis.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 29 citations in OpenAlex.
- PARG inhibition in ATM-deficient prostate cancer: from mechanistic discovery to therapeutic potential.Journal of translational medicine · 2026Article
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- G9a controls plasma cell differentiation through FOXO1 and ETS1 binding site regulatory networks.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- HACD3 promotes malignant progression of NSCLC by suppressing the MKK7/MAPK10 signaling axis.BMC cancer · 2025Article
- VHL-Mediated SYT11 Degradation Suppresses Gastric Cancer Cell Growth and Invasion Through Downregulation of SPINK1.Journal of cellular and molecular medicine · 2025Article
- Constructing a Novel Amino Acid Metabolism Signature: A New Perspective on Pheochromocytoma Diagnosis, Immune Landscape, and Immunotherapy.Biochemical genetics · 2025Article
- Role of SYT11 in human pan-cancer using comprehensive approaches.European journal of medical research · 2024Article
- JAM3: A prognostic biomarker for bladder cancer via epithelial-mesenchymal transition regulation.Biomolecules & biomedicine · 2024Article
- Article
- TNF-α Secreted from Macrophages Increases the Expression of Prometastatic Integrin αV in Gastric Cancer.International journal of molecular sciences · 2022Article
- Impad1 and Syt11 work in an epistatic pathway that regulates EMT-mediated vesicular trafficking to drive lung cancer invasion and metastasis.Cell reports · 2022Article
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundIdentifying biomarkers related to the diagnosis and treatment of gastric cancer (GC) has not made significant progress due to the heterogeneity of tumors. Genes involved in histological classification and genetic correlation studies are essential to develop an appropriate treatment for GC.
methodsIn vitro and in vivo lentiviral shRNA library screening was performed. The expression of Synaptotagmin (SYT11) in the tumor tissues of patients with GC was confirmed by performing Immunohistochemistry, and the correlation between the expression level and the patient's survival rate was analyzed. Phospho-kinase array was performed to detect Jun N-terminal kinase (JNK) phosphorylation. SYT11, JNK, and MKK7 complex formation was confirmed by western blot and immunoprecipitation assays. We studied the effects of SYT11 on GC proliferation and metastasis, real-time cell image analysis, adhesion assay, invasion assay, spheroid formation, mouse xenograft assay, and liver metastasis.
resultsSYT11 is highly expressed in the stem-like molecular subtype of GC in transcriptome analysis of 527 patients with GC. Moreover, SYT11 is a potential prognostic biomarker for histologically classified diffuse-type GC. SYT11 functions as a scaffold protein, binding both MKK7 and JNK1 signaling molecules that play a role in JNK1 phosphorylation. In turn, JNK activation leads to a signaling cascade resulting in cJun activation and expression of downstream genes angiopoietin-like 2 (ANGPTL2), thrombospondin 4 (THBS4), Vimentin, and junctional adhesion molecule 3 (JAM3), which play a role in epithelial-mesenchymal transition (EMT). SNU484 cells infected with SYT11 shRNA (shSYT11) exhibited reduced spheroid formation, mouse tumor formation, and liver metastasis, suggesting a pro-oncogenic role of SYT11. Furthermore, SYT11-antisense oligonucleotide (ASO) displayed antitumor activity in our mouse xenograft model and was conferred an anti-proliferative effect in SNU484 and MKN1 cells.
conclusionSYT11 could be a potential therapeutic target as well as a prognostic biomarker in patients with diffuse-type GC, and SYT11-ASO could be used in therapeutic agent development for stem-like molecular subtype diffuse GC.
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