ArticleThe Journal of clinical investigation2010
Gankyrin plays an essential role in Ras-induced tumorigenesis through regulation of the RhoA/ROCK pathway in mammalian cells.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 67 citations in OpenAlex.
- Gankyrin-Protein Interactions in GI Cancers: A Novel Target of New Therapeutics.Chronic diseases and translational medicine · 2025Review
- LincRNA-miR interactions in hepatocellular carcinoma: comprehensive review and in silico analysis: a step toward ncRNA precision.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Structural modification of the propyl linker of cjoc42 in combination with sulfonate ester and triazole replacements for enhanced gankyrin binding and anti-proliferative activity.Bioorganic & medicinal chemistry · 2024Article
- Rho-Associated Protein Kinase Activity Is Required for Tissue Homeostasis in theJournal of developmental biology · 2024Article
- Gankyrin inhibits ferroptosis through the p53/SLC7A11/GPX4 axis in triple-negative breast cancer cells.Scientific reports · 2023Article
- Small-Molecule Gankyrin Inhibition as a Therapeutic Strategy for Breast and Lung Cancer.Journal of medicinal chemistry · 2022Article
- Gankyrin modulated non-small cell lung cancer progression via glycolysis metabolism in a YAP1-dependent manner.Cell death discovery · 2022Article
- Article
- Gankyrin as Potential Biomarker for Colorectal Cancer With Occult Liver Metastases.Frontiers in oncology · 2021Article
- Quantitative expression of Ikaros, IRF4, and PSMD10 proteins predicts survival in VRD-treated patients with multiple myeloma.Blood advances · 2020Article
- p28GANK overexpression is associated with chemotherapy resistance and poor prognosis in ovarian cancer.Oncology letters · 2020Article
- Small-Molecule Inhibitors of the Proteasome's Regulatory Particle.Chembiochem : a European journal of chemical biology · 2019Review
- The long non-coding RNA Linc-GALH promotes hepatocellular carcinoma metastasis via epigenetically regulating Gankyrin.Cell death & disease · 2019Article
- RACK1 Promotes Self-Renewal and Chemoresistance of Cancer Stem Cells in Human Hepatocellular Carcinoma through Stabilizing Nanog.Theranostics · 2019Article
- Gankyrin is a novel biomarker for disease progression and prognosis of patients with renal cell carcinoma.EBioMedicine · 2019Article
- Gankyrin as a potential target for tumor therapy: evidence and perspectives.American journal of translational research · 2018Review
- The oncoprotein gankyrin promotes the development of colitis-associated cancer through activation of STAT3.Oncotarget · 2017Article
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- Activation of HERV-K Env protein is essential for tumorigenesis and metastasis of breast cancer cells.Oncotarget · 2016Article
- Gankyrin sustains PI3K/GSK-3β/β-catenin signal activation and promotes colorectal cancer aggressiveness and progression.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activating mutations in Ras proteins are present in about 30% of human cancers. Despite tremendous progress in the study of Ras oncogenes, many aspects of the molecular mechanisms underlying Ras-induced tumorigenesis remain unknown. Through proteomics analysis, we previously found that the protein Gankyrin, a known oncoprotein in hepatocellular carcinoma, was upregulated during Ras-mediated transformation, although the functional consequences of this were not clear. Here we present evidence that Gankyrin plays an essential role in Ras-initiated tumorigenesis in mouse and human cells. We found that the increased Gankyrin present following Ras activation increased the interaction between the RhoA GTPase and its GDP dissociation inhibitor RhoGDI, which resulted in inhibition of the RhoA effector kinase Rho-associated coiled coil-containing protein kinase (ROCK). Importantly, Gankyrin-mediated ROCK inhibition led to prolonged Akt activation, a critical step in activated Ras-induced transformation and tumorigenesis. In addition, we found that Gankyrin is highly expressed in human lung cancers that have Ras mutations and that increased Gankyrin expression is required for the constitutive activation of Akt and tumorigenesis in these lung cancers. Our findings suggest that Gankyrin is a key regulator of Ras-mediated activation of Akt through inhibition of the downstream RhoA/ROCK pathway and thus plays an essential role in Ras-induced tumorigenesis.
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