ArticleCancer science2019
Cullin-3/KCTD10 E3 complex is essential for Rac1 activation through RhoB degradation in human epidermal growth factor receptor 2-positive breast cancer cells.
Article in Cancer science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- E3 Ubiquitin Ligases in Breast Cancer Metastasis: A Systematic Review of Pathogenic Functions and Clinical Implications.Frontiers in oncology · 2021Pooled it
- Non-canonical and constitutive activation of small GTPases: more than an exception to the rule?The Biochemical journal · 2026Review
- Elucidating the role of KCTD10 in coronary atherosclerosis: Harnessing bioinformatics and machine learning to advance understanding.Scientific reports · 2025Article
- Aryl Hydrocarbon Receptor (AHR) Suppresses Arsenic (AsInternational journal of biological sciences · 2025Article
- KCTD10 inhibits lung cancer metastasis and angiogenesis via ubiquitin-mediated β-catenin degradation.Frontiers in immunology · 2025Article
- Article
- Mevalonate pathway inhibition reduces bladder cancer metastasis by modulating RhoB protein stability and integrin β1 localization.Communications biology · 2024Article
- Prognostic potential of CUL3 ligase with differential roles in luminal A and basal type breast cancer tumors.Scientific reports · 2024Article
- KCTD10 regulates brain development by destabilizing brain disorder-associated protein KCTD13.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A Comprehensive Analysis of the Structural Recognition between KCTD Proteins and Cullin 3.International journal of molecular sciences · 2024Article
- BTB protein family and human breast cancer: signaling pathways and clinical progress.Journal of cancer research and clinical oncology · 2023Review
- Comprehensive analysis of KCTD family genes associated with hypoxic microenvironment and immune infiltration in lung adenocarcinoma.Scientific reports · 2022Article
- KCTD15 Is Overexpressed in her2+ Positive Breast Cancer Patients and Its Silencing Attenuates Proliferation in SKBR3 CELL LINE.Diagnostics (Basel, Switzerland) · 2022Article
- STK25 and MST3 Have Overlapping Roles to Regulate Rho GTPases during Cortical Development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Why do platelets express KPlatelets · 2021Review
- CNKSR1 serves as a scaffold to activate an EGFR phosphatase via exclusive interaction with RhoB-GTP.Life science alliance · 2021Article
- The emerging role of the KCTD proteins in cancer.Cell communication and signaling : CCS · 2021Review
- Regulation of Rho GTPases in the Vasculature by Cullin3-Based E3 Ligase Complexes.Frontiers in cell and developmental biology · 2021Review
- Cullin3-TNFAIP1 E3 Ligase Controls Inflammatory Response in Hepatocellular Carcinoma Cells via Ubiquitination of RhoB.Frontiers in cell and developmental biology · 2021Article
- From miRNA Target Gene Network to miRNA Function: miR-375 Might Regulate Apoptosis and Actin Dynamics in the Heart Muscle via Rho-GTPases-Dependent Pathways.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Rho GTPase Rac1 is a central regulator of F-actin organization and signal transduction to control plasma membrane dynamics and cell proliferation. Dysregulated Rac1 activity is often observed in various cancers including breast cancer and is suggested to be critical for malignancy. Here, we showed that the ubiquitin E3 ligase complex Cullin-3 (CUL3)/KCTD10 is essential for epidermal growth factor (EGF)-induced/human epidermal growth factor receptor 2 (HER2)-dependent Rac1 activation in HER2-positive breast cancer cells. EGF-induced dorsal membrane ruffle formation and cell proliferation that depends on both Rac1 and HER2 were suppressed in CUL3- or KCTD10-depleted cells. Mechanistically, CUL3/KCTD10 ubiquitinated RhoB for degradation, another Rho GTPase that inhibits Rac1 activation at the plasma membrane by suppressing endosome-to-plasma membrane traffic of Rac1. In HER2-positive breast cancers, high expression of Rac1 mRNA significantly correlated with poor prognosis of the patients. This study shows that this novel molecular axis (CUL3/KCTD10/RhoB) positively regulates the activity of Rac1 in HER2-positive breast cancers, and our findings may lead to new treatment options for HER2- and Rac1-positive breast cancers.
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Registered trials
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 Socratic graph.