ArticleInternational journal of biological sciences2015
Tamoxifen inhibits ER-negative breast cancer cell invasion and metastasis by accelerating Twist1 degradation.
Article in International journal of biological sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- Atorvastatin pre-exposure in hypercholesterolemia remedies 27HC mediated dendritic cell dysfunctions in triple-negative breast cancer.Molecular therapy. Oncology · 2026Article
- ERα-Independent Activity of Tamoxifen-Based Transition Metal Hybrids in Triple-Negative Breast Cancer Models In Vitro and In Vivo.Molecules (Basel, Switzerland) · 2026Article
- Comparative Investigation of Cytotoxic Effects of Structurally Diverse Small Molecules and In Silico Analysis of 1-Acetyl-4-(4-Hydroxyphenyl)piperazine.Journal of cellular and molecular medicine · 2026Article
- Transcription Factors and Methods for the Pharmacological Correction of Their Activity.International journal of molecular sciences · 2025Review
- Signaling Dynamics in Osteogenesis: Unraveling Therapeutic Targets for Bone Generation.Current drug targets · 2025Review
- Repurposing Tamoxifen for Tumor Microenvironment Priming and Enhanced Tumor-Targeted Drug Delivery.Advanced therapeutics · 2023Article
- Maternal tamoxifen exposure leads to abnormal primordial follicle assembly.Histochemistry and cell biology · 2023Article
- Tamoxifen Twists Again: On and Off-Targets in Macrophages and Infections.Frontiers in pharmacology · 2022Review
- Triptonide effectively inhibits triple-negative breast cancer metastasis through concurrent degradation of Twist1 and Notch1 oncoproteins.Breast cancer research : BCR · 2021Article
- Tamoxifen suppresses brain metastasis of estrogen receptor-deficient breast cancer by skewing microglia polarization and enhancing their immune functions.Breast cancer research : BCR · 2021Article
- Metformin Restores the Drug Sensitivity of MCF-7 Cells Resistant Derivates via the Cooperative Modulation of Growth and Apoptotic-Related Pathways.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Targeting disseminated estrogen-receptor-positive breast cancer cells in bone marrow.Oncogene · 2020Article
- HIF-1α, TWIST-1 and ITGB-1, associated with Tumor Stiffness, as Novel Predictive Markers for the Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer.Cancer management and research · 2020Article
- A Bioreductive Prodrug of Cucurbitacin B Significantly Inhibits Tumor Growth in the 4T1 Xenograft Mice Model.ACS medicinal chemistry letters · 2019Article
- Article
- Targeting Twist expression with small molecules.MedChemComm · 2017Review
- Effects of letrozole on breast cancer micro-metastatic tumor growth in bone and lung in mice inoculated with murine 4T1 cells.Clinical & experimental metastasis · 2016Article
- The Small C-terminal Domain Phosphatase 1 Inhibits Cancer Cell Migration and Invasion by Dephosphorylating Ser(P)68-Twist1 to Accelerate Twist1 Protein Degradation.The Journal of biological chemistry · 2016Article
- Tamoxifen Action in ER-Negative Breast Cancer.Signal transduction insights · 2016Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Twist1 is a transcription factor driving epithelial-mesenchymal transition, invasion and metastasis of breast cancer cells. Mice with germ-line Twist1 knockout are embryonic lethal, while adult mice with inducible Twist1 knockout have no obvious health problems, suggesting that Twist1 is a viable therapeutic target for the inhibition of invasion and metastasis of breast cancer in adult patients. In this study, we expressed a luciferase protein or a Twist1-luciferase fusion protein in HeLa cells as part of a high throughput system to screen 1280 compounds in the Library of Pharmacologically Active Compounds (LOPAC) from Sigma-Aldrich for their effects on Twist1 protein expression. One of the most interesting compounds identified is tamoxifen, a selective estrogen receptor (ER) modulator used to treat ER-positive breast cancer. Tamoxifen treatment significantly accelerated Twist1 degradation in multiple cell lines including HEK293 human kidney cells, 4T1 and 168FARN mouse mammary tumor cells with either ectopically or endogenously expressed Twist1. Tamoxifen-induced Twist1 degradation could be blocked by the MG132 proteasome inhibitor, suggesting that tamoxifen induces Twist1 degradation through the ubiquitination-proteasome pathway. However, tamoxifen-induced Twist1 degradation was independent of Twist1 mRNA expression, estrogen signaling and MAPK-mediated Twist1 phosphorylation in these cells. Importantly, tamoxifen also significantly inhibited invasive behavior in Matrigel and lung metastasis in SCID-bg mice of ER-negative 4T1 mammary tumor cells, which depend on endogenous Twist1 to invade and metastasize. These results indicate that tamoxifen can significantly accelerate Twist1 degradation to suppress cancer cell invasion and metastasis, suggesting that tamoxifen can be used not only to treat ER-positive breast cancers but also to reduce Twist1-mediated invasion and metastasis in ER-negative breast cancers.
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Registered trials
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