ArticleJournal of experimental & clinical cancer research : CR2021
Empty spiracles homeobox genes EMX1 and EMX2 regulate WNT pathway activation in sarcomagenesis.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 12 citations in OpenAlex.
- Addressing the Limits of Emx2 Therapy of Glioblastoma Multiforme by Transgene Insulation and Epigenetic Pharmacological Intervention.Biomedicines · 2026Article
- Repurposing Camellia sinensis Roots and Ginkgo biloba Leaves for Multiple Myeloma via Wnt/β-Catenin-Dependent Cell Cycle Arrest and Apoptosis.Chemistry & biodiversity · 2026Article
- Review
- Decoding Sarcoma Drug Resistance: From Molecular Mechanisms to Precision Interventions.Anti-cancer agents in medicinal chemistry · 2026Review
- AKR1B1 is Required for Maintaining Acute Leukemia Cell Survival by Epigenetic Silencing of Tumor Suppressor Genes.Biochemical genetics · 2025Article
- Lnc5q21.2, a novel long intergenic RNA, sensitizes colorectal cancer cells to ATR inhibitor by activating Wnt pathway.Journal of translational internal medicine · 2025Article
- Onco-Ontogeny of Squamous Cell Cancer of the First Pharyngeal Arch Derivatives.International journal of molecular sciences · 2024Review
- CRISPR/dCas9-Mediated DNA Methylation Editing onInternational journal of molecular sciences · 2024Article
- Long Noncoding RNA EMX2-AS Facilitates Osteoblast Differentiation and Bone Formation by Inhibiting EMX2 Protein Translation and Activating Wnt/Stem cells international · 2024Article
- DNA methylation-activated full-length EMX1 facilitates metastasis through EMX1-EGFR-ERK axis in hepatocellular carcinoma.Cell death & disease · 2023Article
- KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11.Open medicine (Warsaw, Poland) · 2023Article
- EMX1 functions as a tumor inhibitor in spinal cord glioma through transcriptional suppression of WASF2 and inactivation of the Wnt/β-catenin axis.Brain and behavior · 2022Article
- Genetic Regulation of Vertebrate Forebrain Development by Homeobox Genes.Frontiers in neuroscience · 2022Review
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundSarcomas are a very heterogeneous group of tumors with intrinsic developmental programs derived from the cell of origin. This implies a functional hierarchy inside tumors governed by sarcoma stem cells. Therefore, genetic and/or epigenetic changes profoundly affect the biology of sarcoma tumor stem cells. EMX genes are proposed to be transcription factors that are involved in the sarcomagenesis process, regardless of the neural or mesodermal embryological sarcoma origin. It has been shown that EMX1 or EMX2 overexpression reduces tumorigenic properties, while reducing the levels of these genes enhances these properties. Furthermore, it has been shown that EMX genes decrease the expression of stem cell regulatory genes and the stem cell phenotype. Taken together, these results indicate that the EMX1 and EMX2 genes negatively regulate these tumor-remodeling populations or sarcoma stem cells, acting as tumor suppressors in sarcoma.
methodsBioinformatic analysis, quantitative mRNA and protein expression analysis, cell models of sarcoma by ectopic expression of EMX genes. By cell biology methods we measured tumorigenesis and populations enriched on stem cell phenotypes, either in vitro or in vivo.
resultsIn this work, we showed that the canonical Wnt pathway is one of the mechanisms that explains the relationships of EMX1/EMX2 and stem cell genes in sarcoma. The Wnt-EMX1/EMX2 relationship was validated in silico with sarcoma patient datasets, in vitro in primary derived sarcoma cell lines, and in vivo. EMX expression was found to negatively regulate the Wnt pathway. In addition, the constitutive activation of the Wnt pathway revers to a more aggressive phenotype with stem cell properties, and stemness gene transcription increased even in the presence of EMX1 and/or EMX2 overexpression, establishing the relationship among the Wnt pathway, stem cell genes and the EMX transcription factors.
conclusionsOur data showed that Empty Spiracles Homeobox Genes EMX1 and EMX2 represses WNT signalling and activation of WNT pathway bypass EMX-dependent stemness repression and induces sarcomagenesis. These results also suggest the relevance of the Wnt/b-catenin/stemness axis as a therapeutic target in sarcoma.
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