ArticleCell communication and signaling : CCS2023
RNF173 suppresses RAF/MEK/ERK signaling to regulate invasion and metastasis via GRB2 ubiquitination in Hepatocellular Carcinoma.
Article in Cell communication and signaling : CCS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 20 citations in OpenAlex.
- Rewiring KRAS-driven cancers through the ubiquitin-proteasome system: therapeutic opportunities with a focus on deubiquitinase.Experimental & molecular medicine · 2026Review
- Identifying expression and DNA methylation biomarkers for lung adenocarcinoma risk in East Asia.Journal of the National Cancer Institute · 2026Article
- Tumor capsule status modifies the survival impact of anatomical versus non-anatomical hepatectomy in early-stage hepatocellular carcinoma: a multicenter retrospective study.World journal of surgical oncology · 2026Article
- Identification and Validation of the Prognostic Value of PTTG1-Related Genes in Hepatocellular Carcinoma by Mendelian Randomization and Single-Cell Transcriptome Analysis.Iranian journal of biotechnology · 2026Article
- Ginsenoside-Rh2 inhibits U251 glioma cell migration and invasion via the Gab2/Akt2 pathway.Frontiers in oncology · 2026Article
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Targeting Kinase Suppressor of Ras 1 (KSR1) for Cancer Therapy.Pharmaceutics · 2025Review
- Bufalin inhibits hepatocellular carcinoma progression by blocking EGFR-mediated RAS-RAF-MEK-ERK pathway activation.Journal of experimental & clinical cancer research : CR · 2025Article
- Ubiquitination in hepatocellular carcinoma immunity.Journal of translational medicine · 2025Review
- MARCH8 suppresses hepatocellular carcinoma by promoting SREBP1 degradation and modulating fatty acid de novo synthesis.Cell death & disease · 2025Article
- [Study on the correlation between high expression of GIT1 and M2 macrophage infiltration and prognosis in hepatocellular carcinoma].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Article
- FBXO32 ubiquitination of SUFU promotes progression and lenvatinib resistance in hepatocellular carcinoma via hedgehog signaling.Medical oncology (Northwood, London, England) · 2025Article
- ROR1 facilitates glioblastoma growth via stabilizing GRB2 to promote c-Fos expression in glioma stem cells.Neuro-oncology · 2025Article
- Deep learning for hepatocellular carcinoma recurrence before and after liver transplantation: a multicenter cohort study.Scientific reports · 2025Article
- Periostin-integrin signaling in hepatocellular carcinoma: from biological function to clinical application.Frontiers in cell and developmental biology · 2025Review
- Identification of Grb2 protein as a potential mediator of macrophage activation in acute pancreatitis based on bioinformatics and experimental verification.Frontiers in immunology · 2025Article
- Identification of potential biomarkers for hepatocellular carcinoma based on machine learning and bioinformatics analysis.Discover oncology · 2024Article
- Degradation of PARP1 by MARCHF3 in tumor cells triggers cCAS-STING activation in dendritic cells to regulate antitumor immunity in hepatocellular carcinoma.Journal for immunotherapy of cancer · 2024Article
- RNF19A inhibits bladder cancer progression by regulating ILK ubiquitination and inactivating the AKT/mTOR signalling pathway.Biology direct · 2024Article
- Signaling, cancer cell plasticity, and intratumor heterogeneity.Cell communication and signaling : CCS · 2024Article
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15 authors at 3 institutions in 1 country.
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Abstract
backgroundThe role of the membrane-associated RING-CH (MARCH) family in carcinogenesis has been widely studied, but the member of this family, RNF173, has not yet been thoroughly explored in the context of hepatocellular carcinoma (HCC).
methodsWith the use of an HCC tissue microarray and IHC staining, we aim to determine the differential expression of RNF173 in HCC patients and its clinical significance. The biological role of RNF173 is investigated through in vitro and in vivo experiments. RNA sequencing, mass spectrometry, and immunoprecipitation are performed to uncover the underlying mechanism of RNF173's impact on the development of HCC.
resultsThe mRNA and protein levels of RNF173 were significantly lower in HCC tissues than in normal tissues. HCC patients with low RNF173 expression had shorter overall survival and recurrence-free survival, and RNF173 was significantly correlated with tumor number, tumor capsule, tumor differentiation, and BCLC stage. In addition, in vitro and in vivo experiments showed that RNF173 downregulation exacerbated tumor progression, including migration, invasion, and proliferation. GRB2 is a key molecule in the RAF/MEK/ERK pathway. RNF173 inhibits the RAF/MEK/ERK signaling by ubiquitinating and degrading GRB2, thereby suppressing HCC cell proliferation, invasion and migration. Combining clinical samples, we found that HCC patients with high RNF173 and low GRB2 expression had the best prognosis.
conclusionRNF173 inhibits the invasion and metastasis of HCC by ubiquitinating and degrading GRB2, thereby suppressing the RAF/MEK/ERK signaling pathway. RNF173 is an independent risk factor for the survival and recurrence of HCC patients. RNF173 may serve as a novel prognostic molecule and potential therapeutic target for HCC. Video Abstract Graphical abstract Model of RNF173 on RAF/MEK/ERK signaling. RNF173 knockdown resulted in impaired ubiquitination and degradation of GRB2, leading to the activation of the RAF/MEK/ERK signaling pathway and promotion of invasion and metastasis in HCC cells.
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