ArticleThe Journal of biological chemistry2015
Aberrant Retinoblastoma (RB)-E2F Transcriptional Regulation Defines Molecular Phenotypes of Osteosarcoma.
Article in The Journal of biological chemistry, 2015. 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, 36 citations in OpenAlex.
- Younger Age Is Associated with Favorable Outcomes in Adult Dogs with Hemangiosarcoma Receiving Adjuvant Doxorubicin Chemotherapy: Results from the PRO-DOX Study.Research square · 2025Article
- WWOX promotes osteosarcoma development via upregulation of Myc.Cell death & disease · 2024Article
- Distinct mechanisms of PTEN inactivation in dogs and humans highlight convergent molecular events that drive cell division in the pathogenesis of osteosarcoma.Cancer genetics · 2023Article
- Gold Nanoparticles Inhibit Extravasation of Canine Osteosarcoma Cells in the Ex Ovo Chicken Embryo Chorioallantoic Membrane Model.International journal of molecular sciences · 2023Article
- Article
- Development of an exosomal gene signature to detect residual disease in dogs with osteosarcoma using a novel xenograft platform and machine learning.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Article
- Associations of Socioeconomic Status, Public vs Private Insurance, and Race/Ethnicity With Metastatic Sarcoma at Diagnosis.JAMA network open · 2020Article
- Beyond What Your Retina Can See: Similarities of Retinoblastoma Function between Plants and Animals, from Developmental Processes to Epigenetic Regulation.International journal of molecular sciences · 2020Review
- A comparison of risk factors for metastasis at diagnosis in humans and dogs with osteosarcoma.Cancer medicine · 2019Article
- HACE1 is a potential tumor suppressor in osteosarcoma.Cell death & disease · 2019Article
- Comparative Transcriptome Analysis Quantifies Immune Cell Transcript Levels, Metastatic Progression, and Survival in Osteosarcoma.Cancer research · 2018Article
- Association of MMP-2, RB and PAI-1 with decreased recurrence-free survival and overall survival in bladder cancer patients.Oncotarget · 2017Article
- Evaluation of P16 expression in canine appendicular osteosarcoma.BMC veterinary research · 2017Article
- Safe and Effective Sarcoma Therapy through Bispecific Targeting of EGFR and uPAR.Molecular cancer therapeutics · 2017Article
- Article
- Heterotypic mouse models of canine osteosarcoma recapitulate tumor heterogeneity and biological behavior.Disease models & mechanisms · 2016Article
- Understanding the Osteosarcoma Pathobiology: A Comparative Oncology Approach.Veterinary sciences · 2016Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 4 countries.
Funding
Abstract
We previously identified two distinct molecular subtypes of osteosarcoma through gene expression profiling. These subtypes are associated with distinct tumor behavior and clinical outcomes. Here, we describe mechanisms that give rise to these molecular subtypes. Using bioinformatic analyses, we identified a significant association between deregulation of the retinoblastoma (RB)-E2F pathway and the molecular subtype with worse clinical outcomes. Xenotransplantation models recapitulated the corresponding behavior for each osteosarcoma subtype; thus, we used cell lines to validate the role of the RB-E2F pathway in regulating the prognostic gene signature. Ectopic RB resets the patterns of E2F regulated gene expression in cells derived from tumors with worse clinical outcomes (molecular phenotype 2) to those comparable with those observed in cells derived from tumors with less aggressive outcomes (molecular phenotype 1), providing a functional association between RB-E2F dysfunction and altered gene expression in osteosarcoma. DNA methyltransferase and histone deacetylase inhibitors similarly reset the transcriptional state of the molecular phenotype 2 cells from a state associated with RB deficiency to one seen with RB sufficiency. Our data indicate that deregulation of RB-E2F pathway alters the epigenetic landscape and biological behavior of osteosarcoma.
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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.