ArticleOncogene2016
TBX2 represses PTEN in rhabdomyosarcoma and skeletal muscle.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Clinical management and therapeutic development for the rare disease rhabdomyosarcoma.Journal of Cancer · 2026Review
- Exploring the oncogenic roles of T-box transcription factor TBX2 and its potential as a therapeutic target.Biochemical Society transactions · 2025Review
- PAX3-FOXO1 dictates myogenic reprogramming and rhabdomyosarcoma identity in endothelial progenitors.Nature communications · 2023Article
- Review
- TBX2 controls a proproliferative gene expression program in melanoma.Genes & development · 2021Article
- Combined genomic and proteomic approaches reveal DNA binding sites and interaction partners of TBX2 in the developing lung.Respiratory research · 2021Article
- DNA demethylation agent 5azadC downregulates HPV16 E6 expression in cervical cancer cell lines independently of TBX2 expression.Oncology letters · 2020Article
- Role of Histone Deacetylases in Skeletal Muscle Physiology and Systemic Energy Homeostasis: Implications for Metabolic Diseases and Therapy.Frontiers in physiology · 2020Review
- Ultraviolet Radiation and Melanomagenesis: From Mechanism to Immunotherapy.Frontiers in oncology · 2020Review
- Targeting the Oncogenic TBX2 Transcription Factor With Chromomycins.Frontiers in chemistry · 2020Article
- TBX2 Identified as a Potential Predictor of Bone Metastasis in Lung Adenocarcinoma via Integrated Bioinformatics Analyses and Verification of Functional Assay.Journal of Cancer · 2020Article
- E-Cadherin Represses Anchorage-Independent Growth in Sarcomas through Both Signaling and Mechanical Mechanisms.Molecular cancer research : MCR · 2019Article
- TBX3 represses TBX2 under the control of the PRC2 complex in skeletal muscle and rhabdomyosarcoma.Oncogenesis · 2019Article
- Transcriptional repression of the ectodomain sheddase ADAM10 by TBX2 and potential implication for Alzheimer's disease.Cellular and molecular life sciences : CMLS · 2019Article
- Wnt deregulation in rhabdomyosarcoma.Stem cell investigation · 2019Article
- PARP inhibitors affect growth, survival and radiation susceptibility of human alveolar and embryonal rhabdomyosarcoma cell lines.Journal of cancer research and clinical oncology · 2019Article
- Loss of Tbx3 in murine neural crest reduces enteric glia and causes cleft palate, but does not influence heart development or bowel transit.Developmental biology · 2018Article
- Targeting the upstream transcriptional activator of PD-L1 as an alternative strategy in melanoma therapy.Oncogene · 2018Article
- Examining the Genetic Background of Porcine Muscle Growth and Development Based on Transcriptome and miRNAome Data.International journal of molecular sciences · 2018Article
- Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Rhabdomyosarcoma (RMS) is the most frequent soft tissue sarcoma in children that shares many features of developing skeletal muscle. TBX2, a T-box family member, is highly upregulated in tumor cells of both major RMS subtypes where it functions as an oncogene. TBX2 is a repressor that is often overexpressed in cancer cells and functions in bypassing cell growth control, including the repression of the cell cycle regulators p14 and p21. We have found that TBX2 directly represses the tumor-suppressor phosphatase and tensin homolog (PTEN) in both RMS and normal muscle. Exogenous expression of TBX2 in normal muscle cells downregulates PTEN, and depletion or interference with TBX2 in RMS cells upregulates PTEN. Human RMS tumors show high levels of TBX2 and correspondingly low levels of PTEN. The expression of PTEN in clinical RMS samples is relatively uncharacterized, and we establish that suppression of PTEN is a frequent event in both subtypes of RMS. TBX2 represses PTEN by directly binding to the promoter and recruiting the histone deacetylase, HDAC1. RMS cells have high levels of activated AKT owing to the deregulation of phosphoinositide-3 kinase (PI3K) signaling, and depletion or interference with TBX2, which upregulates PTEN, results in a reduction of phospho-AKT. We have also found that the highly related T-box family member TBX3 does not repress PTEN in the muscle lineage. This work suggests that TBX2 is a central component of the PTEN/PI3K/AKT signaling pathway deregulation in RMS cells and that targeting TBX2 in RMS tumors may offer a novel therapeutic approach for RMS.
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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.