ArticleMolecular cancer research : MCR2014
Novel roles for ERK5 and cofilin as critical mediators linking ERα-driven transcription, actin reorganization, and invasiveness in breast cancer.
Article in Molecular cancer research : MCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
36 citing papers in PubMed, 59 citations in OpenAlex.
- Estrogen Receptors and Enzymes Involved in Estrogen Synthesis as Breast Cancer Treatment Targets.International journal of molecular sciences · 2026Review
- [High expression of CFL1 and phospho-CFL1 predicts poor prognosis and promotes migration of colon cancer cellsNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Targeting the Extracellular Signal-Regulated Kinase 5-Cellular Jun-Vimentin Axis to Inhibit Epithelial-Mesenchymal Transition and Metastasis in Patients with Triple-Negative Breast Cancer.International journal of medical sciences · 2026Article
- Plasma Circular RNAs in Breast Cancer: From Biomarker Potential to Functional Significance.Cancer reports (Hoboken, N.J.) · 2025Review
- Bone and Extracellular Signal-Related Kinase 5 (ERK5).Biomolecules · 2024Review
- Article
- Immunolocalization of Cytoplasmic ER in ER-negative Breast Carcinoma as a Potent Favorable Prognostic Predictor.Acta histochemica et cytochemica · 2023Article
- A Basic Review on Estrogen Receptor Signaling Pathways in Breast Cancer.International journal of molecular sciences · 2023Review
- Differentially expressed genes related to lymph node metastasis in advanced laryngeal squamous cell cancers.Oncology letters · 2022Article
- Targeting Metabolic Adaptations in the Breast Cancer-Liver Metastatic Niche Using Dietary Approaches to Improve Endocrine Therapy Efficacy.Molecular cancer research : MCR · 2022Article
- Review
- Calcium and calcium-related proteins in endometrial cancer: opportunities for pharmacological intervention.International journal of biological sciences · 2022Review
- Per- and Polyfluoroalkyl Substance Exposure Combined with High-Fat Diet Supports Prostate Cancer Progression.Nutrients · 2021Article
- Article
- Molecular Mechanisms of Epithelial to Mesenchymal Transition Regulated by ERK5 Signaling.Biomolecules · 2021Review
- Combined Targeting of Estrogen Receptor Alpha and Exportin 1 in Metastatic Breast Cancers.Cancers · 2020Article
- Proteomic Investigation of Malignant Major Salivary Gland Tumors.Head and neck pathology · 2020Article
- Unconventional Estrogen Signaling in Health and Disease.Endocrinology · 2020Review
- Discovery of a Gatekeeper Residue in the C-Terminal Tail of the Extracellular Signal-Regulated Protein Kinase 5 (ERK5).International journal of molecular sciences · 2020Article
- Phosphoproteome Analysis Reveals Estrogen-ER Pathway as a Modulator of mTOR Activity Via DEPTOR.Molecular & cellular proteomics : MCP · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledCancer cell motility and invasiveness are fundamental characteristics of the malignant phenotype and are regulated through diverse signaling networks involving kinases and transcription factors. This study establishes an estrogen receptor (ERα)/MAPK (ERK5)/cofilin (CFL1) network that specifies the degree of breast cancer cell aggressiveness through coupling of actin reorganization and hormone receptor-mediated transcription. Using dominant negative and constitutively active forms, as well as small-molecule inhibitors of extracellular signal-regulated kinase (ERK)5 and MAP-ERK kinase (MEK)5, it was revealed that hormone activation of ERα determined the subcellular localization of ERK5, which functions as a coregulator of ERα-dependent gene transcription. Notably, ERK5 acted in concert with the actin remodeling protein, CFL1, and upon hormone exposure, both localized to active nuclear transcriptional hubs as verified by immunofluorescence and proximity ligation assays. Both ERK5 and CFL1 facilitated PAF1 recruitment to the RNA Pol II complex and both were required for regulation of gene transcription. In contrast, in cells lacking ERα, ERK5 and CFL1 localized to cytoplasmic membrane regions of high actin remodeling, promoting cell motility and invasion, thereby revealing a mechanism likely contributing to the generally poorer prognosis of patients with ERα-negative breast cancer. Thus, this study uncovers the dynamic interplay of nuclear receptor-mediated transcription and actin reorganization in phenotypes of breast cancer aggressiveness. IMPLICATIONS: Identification of the ER/ERK5/CFL1 axis suggests new prognostic biomarkers and novel therapeutic avenues to moderate cancer aggressiveness.
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