ArticlePloS one2014
Wilms' tumor protein induces an epithelial-mesenchymal hybrid differentiation state in clear cell renal cell carcinoma.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Pooled it
- Mapping the transcriptional evolution of human metastatic breast cancer.The Journal of clinical investigation · 2024Article
- Cancer spreading patterns based on epithelial-mesenchymal plasticity.Frontiers in cell and developmental biology · 2024Article
- Single-cell transcriptomes of kidneys in a 6-month-old boy with Denys-Drash syndrome reveal stromal cell heterogeneity in the tumor microenvironment.Clinical kidney journal · 2024Article
- MEF2C and miR-194-5p: New Players in Triple Negative Breast Cancer Tumorigenesis.International journal of molecular sciences · 2023Article
- The Cell Biology of Metastatic Invasion in Pancreatic Cancer: Updates and Mechanistic Insights.Cancers · 2023Review
- The versatile roles of ADAM8 in cancer cell migration, mechanics, and extracellular matrix remodeling.Frontiers in cell and developmental biology · 2023Review
- Network topology metrics explaining enrichment of hybrid epithelial/mesenchymal phenotypes in metastasis.PLoS computational biology · 2022Article
- Construction and validation of a prognostic model for kidney renal clear cell carcinoma based on podocyte-associated genes.Cancer medicine · 2022Article
- Interconnected high-dimensional landscapes of epithelial-mesenchymal plasticity and stemness in cancer.Clinical & experimental metastasis · 2022Review
- A preliminary study on the association between epithelial-mesenchymal transition and circulating tumor cells in renal cell carcinoma.Translational andrology and urology · 2022Article
- Epithelial-mesenchymal transition and its transcription factors.Bioscience reports · 2022Review
- Role of the KEAP1-NRF2 Axis in Renal Cell Carcinoma.Cancers · 2020Review
- Emerging Concepts of Hybrid Epithelial-to-Mesenchymal Transition in Cancer Progression.Biomolecules · 2020Review
- Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis.Translational oncology · 2020Review
- Review
- The P2X7 Receptor in the Maintenance of Cancer Stem Cells, Chemoresistance and Metastasis.Stem cell reviews and reports · 2020Review
- Review
- Hybrid Epithelial/Mesenchymal State in Cancer Metastasis: Clinical Significance and Regulatory Mechanisms.Cells · 2020Review
- The pan-therapeutic resistance of disseminated tumor cells: Role of phenotypic plasticity and the metastatic microenvironment.Seminars in cancer biology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The Wilms' tumor transcription factor (WT1) was originally classified as a tumor suppressor, but it is now known to also be associated with cancer progression and poor prognosis in several malignancies. WT1 plays an essential role in orchestrating a developmental process known as mesenchymal-to-epithelial transition (MET) during kidney development, but also induces the reverse process, epithelial-to-mesenchymal transition (EMT) during heart development. WT1 is not expressed in the adult kidney, but shows elevated expression in clear cell renal cell carcinoma (ccRCC). However, the role of WT1 in this disease has not been characterized. In this study, we demonstrate that WT1 is upregulated in ccRCC cells that are deficient in the expression of the von Hippel-Lindau tumor suppressor protein (VHL). We found that WT1 transcriptionally activated Snail, a master transcriptional repressor that is known to induce EMT. Although Snail represses E-cadherin and induces mesenchymal characteristics, we found partial maintenance of E-cadherin and associated epithelial characteristics in kidney cells and ccRCC cells that express WT1, since WT1 upregulates E-cadherin expression and competes with Snail repression. These findings support a novel paradigm in which WT1 induces an epithelial-mesenchymal hybrid transition (EMHT), characterized by Snail up-regulation with E-cadherin maintenance, a tumor cell differentiation state in which cancer cells keep both EMT and MET characteristics which may promote tumor cell plasticity and tumor progression.
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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.