ArticleCancer gene therapy2021
Transcriptional activators YAP/TAZ and AXL orchestrate dedifferentiation, cell fate, and metastasis in human osteosarcoma.
Article in Cancer gene therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Hippo-YAP/TAZ signaling in gastric cancer: molecular pathogenesis and emerging therapeutic horizons.Medical oncology (Northwood, London, England) · 2026Review
- Molecular and Immune Mechanisms Governing Cancer Metastasis, Including Dormancy, Microenvironmental Niches, and Tumor-Specific Programs.International journal of molecular sciences · 2026Review
- EMT and cancer: what clinicians should know.Nature reviews. Clinical oncology · 2025Review
- Multiple-omics analysis reveals a dedifferentiation-immune loop in intrahepatic cholangiocarcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- Osteosarcoma: current insights and advances.Exploration of targeted anti-tumor therapy · 2025Review
- F-box proteins at the crossroads of ubiquitination and tumor immunity: regulatory networks and immunotherapy strategies.Frontiers in immunology · 2025Review
- Thrombospondin 1 Promotes Cytoskeleton Remodeling, Dedifferentiation, and Pulmonary Metastasis through ITGA1 and ITGA6 in Osteosarcoma.International journal of biological sciences · 2025Article
- Mapping the Single-Cell Differentiation Landscape of Osteosarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors.Signal transduction and targeted therapy · 2024Article
- TCellR2Vec: efficient feature selection for TCR sequences for cancer classification.PeerJ. Computer science · 2024Article
- The Role of TAM Receptors in Bone.International journal of molecular sciences · 2023Review
- Nano-Based Drug Delivery Systems: Potential Developments in the Therapy of Metastatic Osteosarcoma-A Narrative Review.Pharmaceutics · 2023Review
- Chemokine Ligand 2 Promotes Migration in Osteosarcoma by Regulating the miR-3659/MMP-3 Axis.Biomedicines · 2023Article
- Multi-Functional Regulation by YAP/TAZ Signaling Networks in Tumor Progression and Metastasis.Cancers · 2023Review
- Article
- Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment.Bone research · 2023Review
- Unveiling the prognostic implications of RPLP1 upregulation in osteosarcoma.American journal of cancer research · 2023Article
- Molecular mechanisms of osteosarcoma metastasis and possible treatment opportunities.Frontiers in oncology · 2023Review
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 1 country.
Funding
Abstract
Osteosarcoma (OS) is a molecularly heterogeneous, aggressive, poorly differentiated pediatric bone cancer that frequently spreads to the lung. Relatively little is known about phenotypic and epigenetic changes that promote lung metastases. To identify key drivers of metastasis, we studied human CCH-OS-D OS cells within a previously described rat acellular lung (ACL) model that preserves the native lung architecture, extracellular matrix, and capillary network. This system identified a subset of cells-termed derived circulating tumor cells (dCTCs)-that can migrate, intravasate, and spread within a bioreactor-perfused capillary network. Remarkably, dCTCs highly expressed epithelial-to-mesenchymal transition (EMT)-associated transcription factors (EMT-TFs), such as ZEB1, TWIST, and SOX9, which suggests that they undergo cellular reprogramming toward a less differentiated state by coopting the same epigenetic machinery used by carcinomas. Since YAP/TAZ and AXL tightly regulate the fate and plasticity of normal mesenchymal cells in response to microenvironmental cues, we explored whether these proteins contributed to OS metastatic potential using an isogenic pair of human OS cell lines that differ in AXL expression. We show that AXL inhibition significantly reduced the number of MG63.2 pulmonary metastases in murine models. Collectively, we present a laboratory-based method to detect and characterize a pure population of dCTCs, which provides a unique opportunity to study how OS cell fate and differentiation contributes to metastatic potential. Though the important step of clinical validation remains, our identification of AXL, ZEB1, and TWIST upregulation raises the tantalizing prospect that EMT-TF-directed therapies might expand the arsenal of therapies used to combat advanced-stage OS.
Indexed as
Identifiers
33408328PMC8636268W3118785274What OpenQuestion holds
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.