ArticleMolecular oncology2021
SIK2 represses AKT/GSK3β/β-catenin signaling and suppresses gastric cancer by inhibiting autophagic degradation of protein phosphatases.
Article in Molecular oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- The umbilical cord blood exosome MFG-E8 alleviates hypoxic-ischemic encephalopathy brain injury in neonatal rats by restoring autophagy flux and inhibiting ferroptosis through GSK3β/β-catenin signaling.Regenerative therapy · 2025Article
- ATP6V0D2 drives triple-negative breast cancer progression and inhibits cisplatin sensitivity by promoting PHLPP2 lysosomal degradation.iScience · 2025Article
- SIK2-mediated phosphorylation of GABARAPL2 facilitates autophagosome-lysosome fusion and rescues neurodegeneration in an Alzheimer's disease model.Translational neurodegeneration · 2025Article
- Silencing PPP2R1A inhibits the progression of gastric cancer cells.Journal of cancer research and clinical oncology · 2025Article
- Inhibition of Salt-Inducible Kinase 2 Protects Motor Neurons From Degeneration in ALS by Activating Autophagic Flux and Enhancing mTORC1 Activity.CNS neuroscience & therapeutics · 2025Article
- Article
- SIK2 activates the autophagy‒apoptosis pathway through SP1 regulation to inhibit the progression of hepatocellular carcinoma.Frontiers in pharmacology · 2025Article
- Role of circular RNAs in preeclampsia (Review).Experimental and therapeutic medicine · 2024Review
- Targeting SIK3 to modulate hippocampal synaptic plasticity and cognitive function by regulating the transcription of HDAC4 in a mouse model of Alzheimer's disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- MicroRNA-203a inhibits breast cancer progression through the PI3K/Akt and Wnt pathways.Scientific reports · 2024Article
- Roles of salt‑inducible kinases in cancer (Review).International journal of oncology · 2023Review
- Deficiency of salt-inducible kinase 2 (SIK2) promotes immune injury by inhibiting the maturation of lymphocytes.MedComm · 2023Article
- Stem Cell Properties of Gastric Cancer Stem-Like Cells under Stress Conditions Are Regulated via the c-Fos/UCH-L3/β-Catenin Axis.Molecules and cells · 2023Article
- CD58 acts as a tumor promotor in hepatocellular carcinoma via activating the AKT/GSK-3β/β-catenin pathway.Journal of translational medicine · 2023Article
- Girdin acts as an oncogene in gastric cancer by regulating AKT/GSK3β/β-catenin signaling.Functional & integrative genomics · 2023Article
- Discovering Breast Cancer Biomarkers Candidates through mRNA Expression Analysis Based on The Cancer Genome Atlas Database.Journal of personalized medicine · 2022Article
- Targeting Cancer Metabolism Plasticity with JX06 Nanoparticles via Inhibiting PDK1 Combined with Metformin for Endometrial Cancer Patients with Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- FTO-mediated autophagy promotes progression of clear cell renal cell carcinoma via regulating SIK2 mRNA stability.International journal of biological sciences · 2022Article
- Asiaticoside Suppresses Gastric Cancer Progression and Induces Endoplasmic Reticulum Stress through the miR-635/HMGA1 Axis.Journal of immunology research · 2022Article
- SIK2 Improving Mitochondrial Autophagy Restriction Induced by Cerebral Ischemia-Reperfusion in Rats.Frontiers in pharmacology · 2022Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Salt-inducible kinase 2 (SIK2) is an important regulator in various intracellular signaling pathways related to apoptosis, tumorigenesis and metastasis. However, the involvement of SIK2 in gastric tumorigenesis and the functional linkage with gastric cancer (GC) progression remain to be defined. Here, we report that SIK2 was significantly downregulated in human GC tissues, and reduced SIK2 expression was associated with poor prognosis of patients. Overexpression of SIK2 suppressed the migration and invasion of GC cells, whereas knockdown of SIK2 enhanced cell migratory and invasive capability as well as metastatic potential. These changes in the malignant phenotype resulted from the ability of SIK2 to suppress epithelial-mesenchymal transition via inhibition of AKT/GSK3β/β-catenin signaling. The inhibitory effect of SIK2 on AKT/GSK3β/β-catenin signaling was mediated primarily through inactivation of AKT, due to its enhanced dephosphorylation by the upregulated protein phosphatases PHLPP2 and PP2A. The upregulation of PHLPP2 and PP2A was attributable to SIK2 phosphorylation and activation of mTORC1, which inhibited autophagic degradation of these two phosphatases. These results suggest that SIK2 acts as a tumor suppressor in GC and may serve as a novel prognostic biomarker and therapeutic target for this tumor.
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