ArticleEMBO molecular medicine2013
Inhibition of redox/Fyn/c-Cbl pathway function by Cdc42 controls tumour initiation capacity and tamoxifen sensitivity in basal-like breast cancer cells.
Article in EMBO molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Review
- Mutation in CDC42 Gene Set as a Response Biomarker for Immune Checkpoint Inhibitor Therapy.Cancer medicine · 2025Article
- The role of CBL family ubiquitin ligases in cancer progression and therapeutic strategies.Frontiers in pharmacology · 2024Review
- Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.Signal transduction and targeted therapy · 2023Review
- The Role of Mitotic Slippage in Creating a "Female Pregnancy-like System" in a Single Polyploid Giant Cancer Cell.International journal of molecular sciences · 2023Article
- Article
- Article
- The role of E3 ubiquitin ligases in the development and progression of glioblastoma.Cell death and differentiation · 2021Review
- An Overview of Potential Therapeutic Agents Targeting WNT/PCP Signaling.Handbook of experimental pharmacology · 2021Review
- Comprehensive Proteomic Characterization Reveals Subclass-Specific Molecular Aberrations within Triple-negative Breast Cancer.iScience · 2020Article
- Control of antiviral innate immune response by protein geranylgeranylation.Science advances · 2019Article
- Cdc42 Promotes ADSC-Derived IPC Induction, Proliferation, And Insulin Secretion Via Wnt/β-Catenin Signaling.Diabetes, metabolic syndrome and obesity : targets and therapy · 2019Article
- Roles of Small GTPases in Acquired Tamoxifen Resistance in MCF-7 Cells Revealed by Targeted, Quantitative Proteomic Analysis.Analytical chemistry · 2018Article
- Inhibition of the RhoGTPase Cdc42 by ML141 enhances hepatocyte differentiation from human adipose-derived mesenchymal stem cells via the Wnt5a/PI3K/miR-122 pathway: impact of the age of the donor.Stem cell research & therapy · 2018Article
- Targeting Rac and Cdc42 GTPases in Cancer.Cancer research · 2018Review
- The R-Enantiomer of Ketorolac Delays Mammary Tumor Development in Mouse Mammary Tumor Virus-Polyoma Middle T Antigen (MMTV-PyMT) Mice.The American journal of pathology · 2018Article
- Leptin signaling and cancer chemoresistance: Perspectives.World journal of clinical oncology · 2017Article
- Interaction of the Small GTPase Cdc42 with Arginine Kinase Restricts White Spot Syndrome Virus in Shrimp.Journal of virology · 2017Article
- High glucose levels promote the proliferation of breast cancer cells through GTPases.Breast cancer (Dove Medical Press) · 2017Article
- A role for activated Cdc42 in glioblastoma multiforme invasion.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We found that basal-like breast cancer (BLBC) cells use Cdc42 to inhibit function of the redox/Fyn/c-Cbl (RFC) pathway, which normally functions to convert small increases in oxidative status into enhanced degradation of c-Cbl target proteins. Restoration of RFC pathway function by genetic or pharmacological Cdc42 inhibition enabled harnessing of pro-oxidant effects of low µM tamoxifen (TMX) concentrations - concentrations utilized in trials on multiple tumour types - to suppress division and induce death of BLBC cells in vitro and to confer TMX sensitivity in vivo through oestrogen receptor-α-independent mechanisms. Cdc42 knockdown also inhibited generation of mammospheres in vitro and tumours in vivo, demonstrating the additional importance of this pathway in tumour initiating cell (TIC) function. These findings provide a new regulatory pathway that is subverted in cancer cells, a novel means of attacking TIC and non-TIC aspects of BLBCs, a lead molecule (ML141) that confers sensitivity to low µM TMX in vitro and in vivo and also appear to be novel in enhancing sensitivity to a non-canonical mode of action of an established therapeutic agent.
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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 OpenQuestion graph.