ArticleJournal of hepatology2011
Inactivation of Ras GTPase-activating proteins promotes unrestrained activity of wild-type Ras in human liver cancer.
Article in Journal of hepatology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 163 citations in OpenAlex.
- Molecular Signaling Pathways, Regulatory and Coactivator Networks, and Emerging Mechanisms in Hepatocellular Carcinoma.Biomedicines · 2026Review
- Kinase suppressor of Ras 1 (KSR1) promotes liver carcinogenesis via activation of the RAS/RAF/MEK/ERK signaling pathway.JHEP reports : innovation in hepatology · 2025Article
- Review
- Consensus artificial intelligence-driven prognostic signature for predicting the prognosis of hepatocellular carcinoma: a multi-center and large-scale study.NPJ precision oncology · 2025Article
- Integrative analysis of exosomal ncRNAs and their regulatory networks in liver cancer progression.Practical laboratory medicine · 2025Article
- Hypermethylated RASAL1's promotive role in chemoresistance and tumorigenesis of choriocarcinoma was regulated by TET2 but not DNMTs.BMC cancer · 2024Article
- Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives.Signal transduction and targeted therapy · 2024Review
- Therapeutic potential of targeting protein tyrosine phosphatases in liver diseases.Acta pharmaceutica Sinica. B · 2024Review
- Disable 2, A Versatile Tissue Matrix Multifunctional Scaffold Protein with Multifaceted Signaling: Unveiling Role in Breast Cancer for Therapeutic Revolution.Cell biochemistry and biophysics · 2024Review
- Impact of Protein Phosphatase Expressions on the Prognosis of Hepatocellular Carcinoma Patients.ACS omega · 2024Article
- Rasal1 regulates calcium dependent neuronal maturation by modifying microtubule dynamics.Cell & bioscience · 2024Article
- DNMT1 expression partially dictates 5-Azacytidine sensitivity and correlates with RAS/MEK/ERK activity in gastric cancer cells.Epigenetics · 2023Article
- Identification of DUSP4/6 overexpression as a potential rheostat to NRAS-induced hepatocarcinogenesis.BMC cancer · 2023Article
- HCV and HCC Tango-Deciphering the Intricate Dance of Disease: A Review Article.International journal of molecular sciences · 2023Review
- Chimera and Tandem-Repeat Type Galectins: The New Targets for Cancer Immunotherapy.Biomolecules · 2023Review
- PITX1 plays essential functions in cancer.Frontiers in oncology · 2023Review
- Review
- RASSF1A independence and early galectin-1 upregulation in PIK3CA-induced hepatocarcinogenesis: new therapeutic venues.Molecular oncology · 2022Article
- HELLS Is Negatively Regulated by Wild-Type P53 in Liver Cancer by a Mechanism Involving P21 and FOXM1.Cancers · 2022Article
- MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma.Cancers · 2021Review
28 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsAberrant activation of the RAS pathway is ubiquitous in human hepatocarcinogenesis, but the molecular mechanisms leading to RAS induction in the absence of RAS mutations remain under-investigated. We defined the role of Ras GTPase activating proteins (GAPs) in the constitutive activity of Ras signaling during human hepatocarcinogenesis.
methodsThe mutation status of RAS genes and RAS effectors was assessed in a collection of human hepatocellular carcinomas (HCC). Levels of RAS GAPs (RASA1-4, RASAL1, nGAP, SYNGAP1, DAB2IP, and NF1) and the RASAL1 upstream inducer PITX1 were determined by real-time RT-PCR and immunoblotting. The promoter and genomic status of RASAL1, DAB2IP, NF1, and PITX1 were assessed by methylation assays and microsatellite analysis. Effects of RASAL1, DAB2IP, and PITX1 on HCC growth were evaluated by transfection and siRNA analyses of HCC cell lines.
resultsIn the absence of Ras mutations, downregulation of at least one RAS GAP (RASAL1, DAB2IP, or NF1) was found in all HCC samples. Low levels of DAB2IP and PITX1 were detected mostly in a HCC subclass from patients with poor survival, indicating that these proteins control tumor aggressiveness. In HCC cells, reactivation of RASAL1, DAB2IP, and PITX1 inhibited proliferation and induced apoptosis, whereas their silencing increased proliferation and resistance to apoptosis.
conclusionsSelective suppression of RASAL1, DAB2IP, or NF1 RAS GAPs results in unrestrained activation of Ras signaling in the presence of wild-type RAS in HCC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.