ArticleEndocrine-related cancer2011
Inhibition of the Rho GTPase, Rac1, decreases estrogen receptor levels and is a novel therapeutic strategy in breast cancer.
Article in Endocrine-related cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 61 citations in OpenAlex.
- Endocrine therapy reprogramming of breast cancer facilitates metastatic escape via upregulation of P-Rex1/Rac1 signalling.Nature communications · 2026Article
- The role of RAC1 in resistance to targeted therapies in cancer.Small GTPases · 2024Review
- Key mRNAs and lncRNAs of pituitary that affect the reproduction of FecB + + small tail han sheep.BMC genomics · 2024Article
- Identification of female-enriched and disease-associated microglia (FDAMic) contributes to sexual dimorphism in late-onset Alzheimer's disease.Journal of neuroinflammation · 2024Article
- Molecular docking analysis of breast cancer target RAC1B with ligands.Bioinformation · 2024Article
- Article
- 17β-estradiol promotes extracellular vesicle release and selective miRNA loading in ERα-positive breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- RAC1B function is essential for breast cancer stem cell maintenance and chemoresistance of breast tumor cells.Oncogene · 2023Article
- Gene-Level Germline Contributions to Clinical Risk of Recurrence Scores in Black and White Patients with Breast Cancer.Cancer research · 2022Article
- RAC1 plays an essential role in estrogen receptor alpha function in breast cancer cells.Oncogene · 2021Article
- Targeting the cytoskeleton against metastatic dissemination.Cancer metastasis reviews · 2021Review
- Article
- Rac1, A Potential Target for Tumor Therapy.Frontiers in oncology · 2021Review
- Mechanisms for Modulating Anoikis Resistance in Cancer and the Relevance of Metabolic Reprogramming.Frontiers in oncology · 2021Review
- An Overview of Potential Therapeutic Agents Targeting WNT/PCP Signaling.Handbook of experimental pharmacology · 2021Review
- Inter-Individual Variation in Response to Estrogen in Human Breast Explants.Journal of mammary gland biology and neoplasia · 2020Article
- Triptolide Inhibits Breast Cancer Cell Metastasis Through Inducing the Expression of miR-146a, a Negative Regulator of Rho GTPase.Oncology research · 2019Article
- Phosphoproteome Analysis Reveals Estrogen-ER Pathway as a Modulator of mTOR Activity Via DEPTOR.Molecular & cellular proteomics : MCP · 2019Article
- Review
- The role of Rac in tumor susceptibility and disease progression: from biochemistry to the clinic.Biochemical Society transactions · 2018Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Rac1, a Rho GTPase, modulates diverse cellular processes and is hyperactive in some cancers. Estrogen receptor-alpha (ERα) in concert with intracellular signaling pathways regulates genes associated with cell proliferation, tumor development, and breast cancer cell survival. Therefore, we examined the possibility of Rac1 and ERα crosstalk in breast cancer cells. We found that Rac1 enhanced ERα transcriptional activity in breast cancer cells. Vav3, a Rho guanine nucleotide exchange factor that activates Rac1, was an upstream mediator, and P21/Cdc42/Rac1 activating kinase-1 (Pak-1) was a downstream effector of Rac1 enhancement of ERα activity. These results suggest that Rac1 may prove to be a therapeutic target. To test this hypothesis, we used a small molecule Rac inhibitor, EHT 1864, and found that EHT 1864 inhibited ERα transcriptional activity. Furthermore, EHT 1864 inhibited estrogen-induced cell proliferation in breast cancer cells and decreased tamoxifen-resistant breast cancer cell growth. EHT 1864 decreased activity of the promoter of the ERα gene resulting in down-regulation of ERα mRNA and protein levels. Therefore, ERα down-regulation by EHT 1864 is the likely mechanism of EHT 1864-mediated inhibition of ERα activity and estrogen-stimulated breast cancer cell proliferation. Since ERα plays a critical role in the pathogenesis of breast cancer and the Rac inhibitor EHT 1864 down-regulates ERα expression and breast cancer cell proliferation, further investigation of the therapeutic potential of Rac1 targeting in the treatment of breast cancer is warranted.
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