ArticleCarcinogenesis2012
c-Myc expression and MEK1-induced Erk2 nuclear localization are required for TGF-beta induced epithelial-mesenchymal transition and invasion in prostate cancer.
Article in Carcinogenesis, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
- Decoding the Raf-Mek-Erk-Rsk pathway in prostate cancer: from molecular mechanisms to clinical opportunities.British journal of cancer · 2026Review
- C-MYC as a key effector of WNT, PI3K/AKT, MAPK, and TGF-β signaling pathways in regulation of epithelial-mesenchymal transition during tumor metastasis.Cancer cell international · 2026Review
- MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor.BMC cancer · 2023Article
- ADAM12 promotes clear cell renal cell carcinoma progression and triggers EMT via EGFR/ERK signaling pathway.Journal of translational medicine · 2023Article
- Extrachromosomal circular DNA in cancer drug resistance and its potential clinical implications.Frontiers in oncology · 2022Review
- BRD4 regulates key transcription factors that drive epithelial-mesenchymal transition in castration-resistant prostate cancer.Prostate cancer and prostatic diseases · 2021Article
- The role of S100A4 for bone metastasis in prostate cancer cells.BMC cancer · 2021Article
- The contributions of extrachromosomal DNA elements in neoplasm progression.American journal of cancer research · 2021Review
- S100A4 is a Biomarker of Tumorigenesis, EMT, Invasion, and Colonization of Host Organs in Experimental Malignant Mesothelioma.Cancers · 2020Article
- FAM172A inhibits EMT in pancreatic cancer via ERK-MAPK signaling.Biology open · 2020Article
- Musashi2 promotes EGF-induced EMT in pancreatic cancer via ZEB1-ERK/MAPK signaling.Journal of experimental & clinical cancer research : CR · 2020Article
- Hypoxia-Induced Epithelial-Mesenchymal Transition in Cancers: HIF-1α and Beyond.Frontiers in oncology · 2020Review
- Purified Vitexin Compound 1 Inhibits UVA-Induced Cellular Senescence in Human Dermal Fibroblasts by Binding Mitogen-Activated Protein Kinase 1.Frontiers in cell and developmental biology · 2020Article
- COX‑2 promotes epithelial‑mesenchymal transition and migration in osteosarcoma MG‑63 cells via PI3K/AKT/NF‑κB signaling.Molecular medicine reports · 2019Article
- Encircling the regions of the pharmacogenomic landscape that determine drug response.Genome medicine · 2019Article
- MicroRNA-212 Targets Mitogen-Activated Protein Kinase 1 to Inhibit Proliferation and Invasion of Prostate Cancer Cells.Oncology research · 2018Article
- Intracellular and extracellular TGF-β signaling in cancer: some recent topics.Frontiers of medicine · 2018Review
- Calreticulin promotes EGF-induced EMT in pancreatic cancer cells via Integrin/EGFR-ERK/MAPK signaling pathway.Cell death & disease · 2017Article
- Inhibition of c-Myc expression accounts for an increase in the number of multinucleated cells in human cervical epithelial cells.Oncology letters · 2017Article
- Fgf regulates dedifferentiation during skeletal muscle regeneration in adult zebrafish.Cellular signalling · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
Abstract
Understanding the initial mechanisms by which epithelial cells transform to an invasive phenotype is critical to the development of diagnostics that can identify the metastatic potential of cancers as well as therapeutic agents that can prevent metastases. Changes in cellular response to the transforming growth factor-beta (TGF-β) cytokine are known to promote epithelial cell invasion and metastasis in part through induction of epithelial-mesenchymal transitions (EMTs). In this report, we demonstrate that non-metastatic human prostate cancer cell lines of increasing Gleason score can be induced to undergo EMT when treated with TGF-β in combination with epidermal growth factor. Mechanistic studies revealed that in cells stably transfected with activated Ras, TGF-β alone induced EMT and that a Ras-Raf-MEK1, but not MEK2, signaling cascade is necessary and sufficient for Erk2 nuclear localization that works in concert with TGF-β to promote EMT. Furthermore, we show for the first time that expression of the transcription factor c-myc, which is phosphorlyated by Erk2, is required for EMT. Characteristically, EMT involved adoption of a spindle-shaped morphology, loss of E-cadherin and increased expression of Vimentin, Fibronectin and Fibroblast Specific Protein-1 (S100A4). Prostate cells undergoing EMT became invasive and expressed several genes associated with metastasis, including MT-MMP1, MMP-2/9, the MMP-9 homodimer, Slug and Twist2. In sum, we demonstrate a novel mechanism by which non-invasive primary prostate tumor cells transition to an invasive phenotype characteristic of malignant tumor cells in response to TGF-β signaling.
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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.