ArticleOncogene2017
A double-negative feedback loop between EpCAM and ERK contributes to the regulation of epithelial-mesenchymal transition in cancer.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 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
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Epigenetic inactivation of ACAT1 promotes epithelial-mesenchymal transition of clear cell renal cell carcinoma.Genes & genomics · 2022Pooled it
- Targeting the EpCAM-AXL axis to overcome drug resistance in lung cancer.Molecular oncology · 2026Article
- An Integrated Spatial Multi-Omics Workflow for Sequential RNA and Protein Profiling in FFPE Tumor Tissue.Cancer research communications · 2026Article
- Integrated transcriptomic and metabolomic profiling reveals immune-metabolic crosstalk and predictive biomarkers of ligustrazine treatment response in idiopathic pulmonary fibrosis.Journal of translational medicine · 2026Article
- EpCAM supports exit from pluripotency of embryonic stem cells via Eomes.Cell death & disease · 2026Article
- Human Endometriotic Lesion-Derived Small Extracellular Vesicles Impair Macrophage Function in the Peritoneal Microenvironment.Journal of extracellular vesicles · 2026Article
- Landscape of cancer associated EpCAM mutations: molecular modeling, predictive insights and impact on patient survival.BMC cancer · 2025Article
- Transcriptional regulators ensuring specific gene expression and decision-making at high TGFβ doses.Life science alliance · 2025Article
- A single-sEV analysis identifies plasma EPCAMExtracellular vesicles and circulating nucleic acids · 2025Article
- Intracellular domain of epithelial cell adhesion molecule induces Wnt receptor transcription to promote colorectal cancer progression.Journal of biomedical science · 2024Article
- Regulation of the Function and Expression of EpCAM.Biomedicines · 2024Review
- Comprehensive analysis reveals dual biological function roles of EpCAM in kidney renal clear cell carcinoma.Heliyon · 2024Article
- EpCAM tumor specificity and proteoform patterns in urothelial cancer.Journal of cancer research and clinical oncology · 2023Article
- Cytosolic EpCAM cooperates with H-Ras to regulate epithelial to mesenchymal transition through ZEB1.PloS one · 2023Article
- Understanding the versatile roles and applications of EpCAM in cancers: from bench to bedside.Experimental hematology & oncology · 2022Review
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- Anti-cancer therapeutic strategies based on HGF/MET, EpCAM, and tumor-stromal cross talk.Cancer cell international · 2022Review
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Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Epithelial-mesenchymal transition (EMT) is an important biological process that has been implicated in cancer metastasis. Epithelial cell adhesion molecule (EpCAM) is expressed at the basolateral membrane of most normal epithelial cells but is overexpressed in many epithelial cancers. In our studies on the role of EpCAM in cancer biology, we observed that EpCAM expression is decreased in mesenchymal-like primary cancer specimens in vivo and following induction of EMT in cancer cell lines in vitro. Extracellular signal-related kinase (ERK) is a key regulator of EMT. We observed that EpCAM expression is decreased with activation of the ERK pathway in primary cancer specimens in vivo and in cancer cell lines in vitro. In experimental models, growth factor stimulation and/or oncogene-induced ERK2 activation suppressed EpCAM expression, whereas genetic or pharmacological inhibition of the ERK pathway restored EpCAM expression. In detailed studies of the EpCAM promoter region, we observed that ERK2 suppresses EpCAM transcription directly by binding to a consensus ERK2-binding site in the EpCAM promoter and indirectly through activation of EMT-associated transcription factors SNAI1, SNAI2, TWIST1 and ZEB1, which bind to E-box sites in the EpCAM promoter. Surprisingly, EpCAM appears to modulate ERK activity. Using multiple cell lines, we demonstrated that specific ablation of EpCAM resulted in increased ERK pathway activity and SNAI2 expression, migration and invasion, whereas forced expression of EpCAM resulted in decreased ERK pathway activity and SNAI2 expression, migration and invasion. These observations provide important insights into the regulation of EpCAM expression during EMT, demonstrate an unexpected role for EpCAM in the regulation of ERK and define a novel double-negative feedback loop between EpCAM and ERK that contributes to the regulation of EMT. These studies have important translational implications as both EpCAM and ERK are currently being targeted in human clinical trials.
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What OpenQuestion holds
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.