ArticleNature communications2021
Synthetic essentiality between PTEN and core dependency factor PAX7 dictates rhabdomyosarcoma identity.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Pediatric sarcomas: challenges and opportunities.Genes & development · 2026Review
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- Non-cell-autonomous tumor promotion in DICER1 cancer predisposition.Developmental cell · 2026Article
- Secretoglobin 3A1 in activated muscle satellite cells contributes to myosin heavy chain IIX and IIB fiber differentiation.Cellular and molecular life sciences : CMLS · 2025Article
- Synthetic essentiality of TRAIL/TNFSF10 in VHL-deficient renal cell carcinoma.bioRxiv : the preprint server for biology · 2025Article
- The Role of PAX7 in Breast Cancer Prognosis and Its Mechanistic Involvement in the Wnt/β-Catenin Pathway.Journal of cellular and molecular medicine · 2025Article
- miR-497 Target Gene Regulatory Network in Angiosarcoma.Molecular cancer research : MCR · 2024Article
- A comprehensive analysis of minimally differentially methylated regions common to pediatric and adult solid tumors.NPJ precision oncology · 2024Article
- Contemporary preclinical mouse models for pediatric rhabdomyosarcoma: from bedside to bench to bedside.Frontiers in oncology · 2024Article
- Myogenesis gone awry: the role of developmental pathways in rhabdomyosarcoma.Frontiers in cell and developmental biology · 2024Review
- The roles of miRNAs in adult skeletal muscle satellite cells.Free radical biology & medicine · 2023Review
- MicroRNA control of the myogenic cell transcriptome and proteome: the role of miR-16.American journal of physiology. Cell physiology · 2023Article
- Nuclear PTEN's Functions in Suppressing Tumorigenesis: Implications for Rare Cancers.Biomolecules · 2023Review
- The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- A SNAI2/CTCF Interaction is Required forMolecular and cellular biology · 2023Article
- Article
- ERK5 Is a Major Determinant of Chemical Sarcomagenesis: Implications in Human Pathology.Cancers · 2022Article
- Genetic context of oncogenic drivers dictates vascular sarcoma development in aP2-Cre mice.The Journal of pathology · 2022Article
- The perfect PTEN - transcriptional regulation by PTEN dictates sarcoma identity.Molecular & cellular oncology · 2021Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
PTEN promoter hypermethylation is nearly universal and PTEN copy number loss occurs in ~25% of fusion-negative rhabdomyosarcoma (FN-RMS). Here we show Pten deletion in a mouse model of FN-RMS results in less differentiated tumors more closely resembling human embryonal RMS. PTEN loss activated the PI3K pathway but did not increase mTOR activity. In wild-type tumors, PTEN was expressed in the nucleus suggesting loss of nuclear PTEN functions could account for these phenotypes. Pten deleted tumors had increased expression of transcription factors important in neural and skeletal muscle development including Dbx1 and Pax7. Pax7 deletion completely rescued the effects of Pten loss. Strikingly, these Pten;Pax7 deleted tumors were no longer FN-RMS but displayed smooth muscle differentiation similar to leiomyosarcoma. These data highlight how Pten loss in FN-RMS is connected to a PAX7 lineage-specific transcriptional output that creates a dependency or synthetic essentiality on the transcription factor PAX7 to maintain tumor identity.
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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.