ArticleThe Journal of clinical investigation2013
IQGAP1 suppresses TβRII-mediated myofibroblastic activation and metastatic growth in liver.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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The trial behind it
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Who cites it
58 citing papers in PubMed, 92 citations in OpenAlex.
- TUFT1 stabilizes TGF-β receptor II protein and facilitates activation of hepatic stellate cells into metastasis-promoting myofibroblasts.Cell death and differentiation · 2026Article
- New insights into the role of ubiquitination in angiogenesis (Review).International journal of molecular medicine · 2025Review
- CMTM6 mediates the Warburg effect and promotes the liver metastasis of colorectal cancer.Experimental & molecular medicine · 2024Article
- In silico predicted compound targeting the IQGAP1-GRD domain selectively inhibits growth of human acute myeloid leukemia.Scientific reports · 2024Article
- Codelivery of TGFβ and Cox2 siRNA inhibits HCC by promoting T-cell penetration into the tumor and improves response to Immune Checkpoint Inhibitors.NAR cancer · 2024Article
- A Novel Trojan Horse Nanotherapy Strategy Targeting the cPKM-STMN1/TGFB1 Axis for Effective Treatment of Intrahepatic Cholangiocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The IQGAP scaffolds: Critical nodes bridging receptor activation to cellular signaling.The Journal of cell biology · 2023Review
- FOXC2-AS1/FOXC2 axis mediates matrix stiffness-induced trans-differentiation of hepatic stellate cells into fibrosis-promoting myofibroblasts.International journal of biological sciences · 2023Article
- Review
- Targeting FAPα-expressing hepatic stellate cells overcomes resistance to antiangiogenics in colorectal cancer liver metastasis models.The Journal of clinical investigation · 2022Article
- CDC42-IQGAP Interactions Scrutinized: New Insights into the Binding Properties of the GAP-Related Domain.International journal of molecular sciences · 2022Article
- Roles of ubiquitination in the crosstalk between tumors and the tumor microenvironment (Review).International journal of oncology · 2022Review
- Silencing IQGAP1 alleviates hepatic fibrogenesis via blocking bone marrow mesenchymal stromal cell recruitment to fibrotic liver.Molecular therapy. Nucleic acids · 2022Article
- PD-L1 promotes myofibroblastic activation of hepatic stellate cells by distinct mechanisms selective for TGF-β receptor I versus II.Cell reports · 2022Article
- Role of IQ Motif-Containing GTPase-Activating Proteins in Hepatocellular Carcinoma.Frontiers in oncology · 2022Review
- Role of IQGAP1 in Carcinogenesis.Cancers · 2021Review
- Scaffolding Protein IQGAP1 Is Dispensable, but Its Overexpression Promotes Hepatocellular Carcinoma via YAP1 Signaling.Molecular and cellular biology · 2021Article
- Malignant subclone drives metastasis of genetically and phenotypically heterogenous cell clusters through fibrotic niche generation.Nature communications · 2021Article
- Article
- Construction of a Novel Multigene Panel Potently Predicting Poor Prognosis in Patients with Clear Cell Renal Cell Carcinoma.Cancers · 2020Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
In the tumor microenvironment, TGF-β induces transdifferentiation of quiescent pericytes and related stromal cells into myofibroblasts that promote tumor growth and metastasis. The mechanisms governing myofibroblastic activation remain poorly understood, and its role in the tumor microenvironment has not been explored. Here, we demonstrate that IQ motif containing GTPase activating protein 1 (IQGAP1) binds to TGF-β receptor II (TβRII) and suppresses TβRII-mediated signaling in pericytes to prevent myofibroblastic differentiation in the tumor microenvironment. We found that TGF-β1 recruited IQGAP1 to TβRII in hepatic stellate cells (HSCs), the resident liver pericytes. Iqgap1 knockdown inhibited the targeting of the E3 ubiquitin ligase SMAD ubiquitination regulatory factor 1 (SMURF1) to the plasma membrane and TβRII ubiquitination and degradation. Thus, Iqgap1 knockdown stabilized TβRII and potentiated TGF-β1 transdifferentiation of pericytes into myofibroblasts in vitro. Iqgap1 deficiency in HSCs promoted myofibroblast activation, tumor implantation, and metastatic growth in mice via upregulation of paracrine signaling molecules. Additionally, we found that IQGAP1 expression was downregulated in myofibroblasts associated with human colorectal liver metastases. Taken together, our studies demonstrate that IQGAP1 in the tumor microenvironment suppresses TβRII and TGF-β dependent myofibroblastic differentiation to constrain tumor growth.
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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.