ArticleJournal of experimental & clinical cancer research : CR2019
The transcription factor LEF1 promotes tumorigenicity and activates the TGF-β signaling pathway in esophageal squamous cell carcinoma.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- High expression of LEF1 correlates with poor prognosis in solid tumors, but not blood tumors: a meta-analysis.Bioscience reports · 2020Pooled it
- LEF1/NFE2L3/TACC1 axis activates the AKT-mTOR pathway to promote the progression of esophageal squamous cell carcinoma.Journal of thoracic disease · 2026Article
- Identification of a novel signature in progression of non-small cell lung cancer based on HdWGCNA and in vitro validation.BMC medical genomics · 2026Article
- A METTL3-NFE2L3 axis mediates tumor stemness and progression in lung adenocarcinoma.Science advances · 2025Article
- Single-Cell RNA Sequencing Reveals LEF1 as a Prognostic Biomarker for Poor Outcomes in Oxaliplatin-Resistant Colorectal Cancer.Human mutation · 2025Article
- Cancer stem cells in personalized therapy: mechanisms, microenvironment crosstalk, and therapeutic vulnerabilities.Frontiers in cell and developmental biology · 2025Review
- SNAI1 promotes epithelial-mesenchymal transition and maintains cancer stem cell-like properties in thymic epithelial tumors through the PIK3R2/p-EphA2 Axis.Journal of experimental & clinical cancer research : CR · 2024Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Carcinogenesis promotion in oral squamous cell carcinoma: KDM4A complex-mediated gene transcriptional suppression by LEF1.Cell death & disease · 2023Article
- Article
- STAT3-Mediated Promoter-Enhancer Interaction Up-Regulates Inhibitor of DNA Binding 1 (International journal of molecular sciences · 2023Article
- Multiple Germline Events Contribute to Cancer Development in Patients with Li-Fraumeni Syndrome.Cancer research communications · 2023Article
- Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress.Epigenomes · 2023Article
- Potent molecular-targeted therapies for advanced esophageal squamous cell carcinoma.Therapeutic advances in medical oncology · 2023Review
- Review
- Article
- Lateral confined growth of cells activates Lef1 dependent pathways to regulate cell-state transitions.Scientific reports · 2022Article
- Recruitment of LEF1 by Pontin chromatin modifier amplifies TGFBR2 transcription and activates TGFβ/SMAD signalling during gliomagenesis.Cell death & disease · 2022Article
- Exploring YAP1-centered networks linking dysfunctional CFTR to epithelial-mesenchymal transition.Life science alliance · 2022Article
- Construction and validation of a novel prediction system for detection of overall survival in lung cancer patients.World journal of clinical cases · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundEsophageal squamous cell carcinoma (ESCC) is the most difficult subtype of esophageal cancer to treat due to the paucity of effective targeted therapy. ESCC is believed to arise from cancer stem cells (CSCs) that contribute to metastasis and chemoresistance. Despite advances in diagnosis and treatment, the prognosis of ESCC patients remains poor.
methodsIn this study, we applied western blot, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry, RNA-Seq analysis, luciferase reporter assay, Chip-qPCR, bioinformatics analysis, and a series of functional assays to show the potential role of LEF1 in regulating esophageal CSCs.
resultsWe found that the overexpression of LEF1 was associated with aberrant clinicopathological characteristics and the poor prognosis of ESCC patients. In addition, the elevated expression of LEF1 and OV6 was significantly associated with aberrant clinicopathological features, and poor patient prognosis. Moreover, the overexpression of LEF1 was observed in esophageal CSCs purified by the magnetic sorting of adherent and spheroidal ESCC cells. The increased level of LEF1 in CSCs facilitated the expression of CSC markers, stem cell-like properties, resistance to chemotherapy, and tumorigenicity and increased the percentage of CSCs in ESCC samples. Conversely, the knockdown of LEF1 significantly diminished the self-renewal properties of ESCC. We showed that LEF1 played an important mechanical role in activating the TGF-β signaling pathway by directly binding to the ID1 gene promoter. A positive association between LEF1 and ID1 expression was also observed in clinical ESCC samples.
conclusionOur results indicate that the overexpression of LEF1 promotes a CSC-like phenotype in and the tumorigenicity of ESCC by activating the TGF-β signaling pathway. The inhibition of LEF1 might therefore be a novel therapeutic target to inactivate CSCs and inhibit tumor progression.
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Registered trials
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