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RasGAP SH3-domain-Binding Protein 1 (G3BP1) has been implicated in cell growth, migration, and metastasis of some cancers, yet its function in hepatocellular carcinoma (HCC) remains to be explored. In the present study, we reported that G3BP1 was upregulated in HCC tissues compared with adjacent non-cancerous liver tissues both in mRNA and protein levels, and its high expression was significantly correlated with poor prognosis of HCC patients. Functional analyses demonstrated that forced expression of G3BP1 in HCC cells promoted cell migration, and silenced expression of G3BP1 by RNA interference caused opposite effects. Moreover, G3BP1 knockdown attenuated the distant metastasis capacity of HCC cells through tail vein injection approach in nude mice model. At molecular mechanism, we found G3BP1 knockdown decreased Slug expression, and increased the expression of the epithelial cell marker E-cadherin. Overexpression of Slug could restore the phenotype of G3BP1 silencing induced cell migration inhibition. Together, our data establish G3BP1 as an oncogenic factor involved in the metastasis of HCC and suggest that G3BP1 might serve as a novel predictor for patients' outcome.
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FEBS Lett
September 2025
Institute for Integrated Stress Response Signaling, Faculty of Medicine, University Hospital Cologne, Germany.
Amyotrophic lateral sclerosis (ALS) is a fatal disorder caused by motor neuron degeneration. Hexanucleotide repeat expansions in the C9orf72 gene, the most common genetic cause of ALS (C9-ALS), drive toxicity through different mechanisms. These pathological changes include alterations in stress granules (SGs), ribonucleoprotein complexes formed under stress conditions.
View Article and Find Full Text PDFBone Res
August 2025
Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Osteosarcoma (OS) is the most frequent primary bone sarcomas with high recurrence and poor prognosis. Emerging evidence indicates that membraneless organelles stress granules (SGs), whose assemblies are driven by scaffold protein G3BP1, are extensively involved in tumor, especially in OS. However, how SGs behave and communicate with organelles, particularly nucleoli and mitochondria, during drug challenges remain unknown.
View Article and Find Full Text PDFAngiogenesis
August 2025
Children's Heart Center, Institute of Cardiovascular Development and Translational Medicine, Zhejiang Provincial Clinical Research Center for Pediatric Disease, the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China.
Vascular permeability, crucial for organ function, relies on the endothelial barrier formed by intercellular junctions (AJs, TJs). However, mechanisms regulating these junctions and maintaining endothelial barrier integrity are incompletely understood. Here, we investigate the RNA-binding protein G3BP1's role in endothelial barrier integrity using G3bp1 knockout mice and G3BP1-deficient human endothelial cells.
View Article and Find Full Text PDFBiochem Pharmacol
August 2025
School of Life Science, Beijing Institute of Technology, Beijing 100081, China; Advanced Technology Research Institute, Beijing Institute of Technology, Jinan 250307, China. Electronic address:
USP10 is a critical deubiquitinating enzyme within the ubiquitin-specific protease family, playing multifaceted roles in cellular physiology and disease pathogenesis. Structurally composed of a G3BP1-interacting motif, a N-terminal domain (mediating most protein interactions), and a catalytic USP domain (residues 415-795, catalytic triad C424-H736-D751), USP10 regulates diverse cellular pathways by stabilizing key proteins through deubiquitination. It exhibits context-dependent functional duality, particularly in cancer: USP10 promotes tumorigenesis in various cancers (e.
View Article and Find Full Text PDFNat Commun
August 2025
Department of Nutrition and Health, Key Laboratory of Functional Dairy, China Agricultural University, Beijing, China.
Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are two common liver disorders characterized by abnormal lipid accumulation. Our study found reduced levels of GTPase-activating protein-binding protein1 (G3BP1) in patients with MASLD and MASH, suggesting its involvement in these liver disorders. Hepatocyte-specific G3BP1 knockout (G3BP1 HKO) male mice had more severe MASLD and MASH than their corresponding controls.
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