ArticleThe Journal of cell biology2002
Ras and TGF[beta] cooperatively regulate epithelial cell plasticity and metastasis: dissection of Ras signaling pathways.
Article in The Journal of cell biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 329 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
329 citing papers in PubMed, 1 synthesis or guideline pooled it, 695 citations in OpenAlex.
- Conservation of Epithelial-to-Mesenchymal Transition Process in Neural Crest Cells and Metastatic Cancer.Cells, tissues, organs · 2021Pooled it
- SMARCA4, STK11, and KEAP1 co-inactivation associates with poor prognosis and upregulation of the TGF-β pathway in lung adenocarcinoma.Translational oncology · 2026Article
- Glioblastoma Subtypes Exhibit Distinct Migration Mechanics and Immune Responses.Cancer research communications · 2026Article
- Multiple distinct metastatic cell states are induced by epithelial-mesenchymal plasticity.bioRxiv : the preprint server for biology · 2026Article
- Single-Cell Profiling Identifies a CCR2Genes · 2026Article
- PCSK5M452I Is a Recessive Hypomorph Exclusive to MCF10DCIS.com Cells.Molecular cancer research : MCR · 2026Article
- Upregulation of RAF and RalGDS gene expression by TGF-β in systemic sclerosis dermal fibroblasts: a controlled in vitro study.Clinical rheumatology · 2026Article
- Evolution of Cancer Metastases via Lineage Trans-Differentiation.Research (Washington, D.C.) · 2026Article
- The atypical KRASMolecular oncology · 2025Article
- GSK-3 and BCL-XL inhibition mitigates the competitive advantage of APC-mutant colorectal cancer cells.Oncogenesis · 2025Article
- Ras-MAPK pathway in patients with lupus nephritis.Lupus science & medicine · 2025Article
- Schwann cells in regeneration and cancer: an epithelial-mesenchymal transition perspective.Open biology · 2025Review
- Article
- Effects of Anti-Fibrotic Drugs on Transcriptome of Peripheral Blood Mononuclear Cells in Idiopathic Pulmonary Fibrosis.International journal of molecular sciences · 2024Article
- Insights into lenvatinib resistance: mechanisms, potential biomarkers, and strategies to enhance sensitivity.Medical oncology (Northwood, London, England) · 2024Review
- Cooperative pro-tumorigenic adaptation to oncogenic RAS through epithelial-to-mesenchymal plasticity.Science advances · 2024Article
- Epithelial-Mesenchymal Transition: A Fundamental Cellular and Microenvironmental Process in Benign and Malignant Prostate Pathologies.Biomedicines · 2024Review
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- A guide to ERK dynamics, part 2: downstream decoding.The Biochemical journal · 2023Article
- Targeting Fatty Acid Amide Hydrolase Counteracts the Epithelial-to-Mesenchymal Transition in Keratinocyte-Derived Tumors.International journal of molecular sciences · 2023Article
269 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multistep carcinogenesis involves more than six discrete events also important in normal development and cell behavior. Of these, local invasion and metastasis cause most cancer deaths but are the least well understood molecularly. We employed a combined in vitro/in vivo carcinogenesis model, that is, polarized Ha-Ras-transformed mammary epithelial cells (EpRas), to dissect the role of Ras downstream signaling pathways in epithelial cell plasticity, tumorigenesis, and metastasis. Ha-Ras cooperates with transforming growth factor beta (TGFbeta) to cause epithelial mesenchymal transition (EMT) characterized by spindle-like cell morphology, loss of epithelial markers, and induction of mesenchymal markers. EMT requires continuous TGFbeta receptor (TGFbeta-R) and oncogenic Ras signaling and is stabilized by autocrine TGFbeta production. In contrast, fibroblast growth factors, hepatocyte growth factor/scatter factor, or TGFbeta alone induce scattering, a spindle-like cell phenotype fully reversible after factor withdrawal, which does not involve sustained marker changes. Using specific inhibitors and effector-specific Ras mutants, we show that a hyperactive Raf/mitogen-activated protein kinase (MAPK) is required for EMT, whereas activation of phosphatidylinositol 3-kinase (PI3K) causes scattering and protects from TGFbeta-induced apoptosis. Hyperactivation of the PI3K pathway or the Raf/MAPK pathway are sufficient for tumorigenesis, whereas EMT in vivo and metastasis required a hyperactive Raf/MAPK pathway. Thus, EMT seems to be a close in vitro correlate of metastasis, both requiring synergism between TGFbeta-R and Raf/MAPK signaling.
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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.