ArticleOncogenesis2021
YWHAE-NUTM2 oncoprotein regulates proliferation and cyclin D1 via RAF/MAPK and Hippo pathways.
Article in Oncogenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Uterine mesenchymal neoplasm harbouring an AKAP9::BRAF fusion: identification of a novel kinase-driven molecular subset.Virchows Archiv : an international journal of pathology · 2026Article
- Non-viral in vivo electroporation-based chromosomal engineering and repair assessment in the murine uterine epithelium.PloS one · 2026Article
- Synergistic epigenetic modulation by 5-aza-2'-deoxycytidine and Wnt3a drives osteogenic trans-differentiation of 3T3-L1 pre-adipocytes throughEpigenomics · 2025Article
- PGRP-S promotes hepatocellular carcinoma progression via MAPK/ERK pathway by interaction with TTC1.Scientific reports · 2025Article
- Geometrically controlled cardiac microtissues promote vascularization and reduce inflammationCell biomaterials · 2025Article
- LncRNA NEAT1 participates in diminished ovarian reserve by affecting granulosa cell apoptosis and estradiol synthesis via the miR-204-5p/ESR1 axis.Journal of ovarian research · 2025Article
- Probiotic-Derived P8 Protein: Promoting Proliferation and Migration in Stem Cells and Keratinocytes.International journal of stem cells · 2025Article
- Molecular Insights in Endometrial Stromal Sarcomas: Exploring New Targets for Novel Therapeutic Approaches.Biomolecules · 2025Review
- Inhibition of lanosterol synthase linking with MAPK/JNK signaling pathway suppresses endometrial cancer.Cell death discovery · 2025Article
- Uterine Mesenchymal Tumors: Updates on Pathology, Molecular Landscape, and Therapeutics.Medicina (Kaunas, Lithuania) · 2024Review
- Targeting low levels of MIF expression as a potential therapeutic strategy for ALS.Cell reports. Medicine · 2024Article
- High-grade endometrial stromal sarcoma withGynecologic oncology reports · 2023Article
- Ultrasensitive proteomics depicted an in-depth landscape for the very early stage of mouse maternal-to-zygotic transition.Journal of pharmaceutical analysis · 2023Article
- Genomic and Transcriptomic Characterization Revealed the High Sensitivity of Targeted Therapy and Immunotherapy in a Subset of Endometrial Stromal Sarcoma.Cancer research and treatment · 2023Article
- Gut microbiota: key facilitator in metastasis of colorectal cancer.Frontiers in oncology · 2023Review
- The Hippo pathway in endometrial cancer: a potential therapeutic target?Frontiers in oncology · 2023Review
- Whole Blood Transcriptional Fingerprints of High-Grade Glioma and Longitudinal Tumor Evolution under Carbon Ion Radiotherapy.Cancers · 2022Article
- β-catenin is a Potential Prognostic Biomarker in Uterine Sarcoma.Technology in cancer research & treatmentArticle
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Endometrial stromal sarcoma (ESS) is the second most common subtype of uterine mesenchymal cancer, after leiomyosarcoma, and oncogenic fusion proteins are found in many ESS. Our previous studies demonstrated transforming properties and diagnostic relevance of the fusion oncoprotein YWHAE-NUTM2 in high-grade endometrial stromal sarcoma (HG-ESS) and showed that cyclin D1 is a diagnostic biomarker in these HG-ESS. However, YWHAE-NUTM2 mechanisms of oncogenesis and roles in cyclin D1 expression have not been characterized. In the current studies, we show YWHAE-NUTM2 complexes with both BRAF/RAF1 and YAP/TAZ in HG-ESS. These interactions are functionally relevant because YWHAE-NUTM2 knockdown in HG-ESS and other models inhibits RAF/MEK/MAPK phosphorylation, cyclin D1 expression, and cell proliferation. Further, cyclin D1 knockdown in HG-ESS dephosphorylates RB1 and inhibits proliferation. In keeping with these findings, we show that MEK and CDK4/6 inhibitors have anti-proliferative effects in HG-ESS, and combinations of these inhibitors have synergistic activity. These findings establish that YWHAE-NUTM2 regulates cyclin D1 expression and cell proliferation by dysregulating RAF/MEK/MAPK and Hippo/YAP-TAZ signaling pathways. Recent studies demonstrate Hippo/YAP-TAZ pathway aberrations in many sarcomas, but this is among the first studies to demonstrate a well-defined oncogenic mechanism as the cause of Hippo pathway dysregulation.
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Registered trials
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