ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
RABL6A Is an Essential Driver of MPNSTs that Negatively Regulates the RB1 Pathway and Sensitizes Tumor Cells to CDK4/6 Inhibitors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 54 citations in OpenAlex.
- Phase II trial of CDK4/6 inhibitor palbociclib in advanced sarcoma based on mRNA expression of CDK4/ CDKN2A.Signal transduction and targeted therapy · 2023Trial
- Advancing neurofibromatosis research: a comparative review of animal models and their utility in dissecting the tumor microenvironment.Laboratory animal research · 2026Review
- Development of a Cre-Inducible Rabl6a Transgenic Mouse Model That Enhances Sarcoma Growth In Vivo.Cancers · 2026Article
- CSF1R inhibitors mitigate CDK4/6 inhibitor-induced immunosuppression to increase antitumor immunity in HR+/HER2- breast cancer.Oncogene · 2026Article
- Antitumor Activity of Sodium Selenite, Palbociclib, and Disulfiram Against Osteosarcoma and Rhabdomyosarcoma Cell Lines.Drug development research · 2026Article
- Review
- Review
- Somatic CRISPR tumorigenesis and multiomic analysis reveal a pentose phosphate pathway disruption vulnerability in MPNSTs.Science advances · 2025Article
- From benign neurofibromas to malignant peripheral nerve sheath tumors (MPNST): a gaming among multiple factors.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Novel Therapeutics and the Path Toward Effective Immunotherapy in Malignant Peripheral Nerve Sheath Tumors.Cancers · 2025Review
- Triple Combination of MEK, BET, and CDK Inhibitors Significantly Reduces Human Malignant Peripheral Nerve Sheath Tumors in Mouse Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Article
- A Sequencing Overview of Malignant Peripheral Nerve Sheath Tumors: Findings and Implications for Treatment.Cancers · 2025Review
- WDR12/RAC1 axis promoted proliferation and anti-apoptosis in colorectal cancer cells.Molecular and cellular biochemistry · 2024Article
- MicroRNA-1307-3p contributes to breast cancer progression through PRM2.Thoracic cancer · 2024Article
- Linking FOXM1 and PD-L1 to CDK4/6-MEK targeted therapy resistance in malignant peripheral nerve sheath tumors.Oncotarget · 2024Review
- Nicotine-induced activation of cholinergic receptor nicotinic alpha 5 subunit mediates the malignant behaviours of laryngeal squamous epithelial cells by interacting with RABL6.Cell death discovery · 2024Article
- CDK4/6 inhibition enhances SHP2 inhibitor efficacy and is dependent upon RB function in malignant peripheral nerve sheath tumors.Science advances · 2023Article
- FOXM1, MEK, and CDK4/6: New Targets for Malignant Peripheral Nerve Sheath Tumor Therapy.International journal of molecular sciences · 2023Review
- Characterizing T-cell dysfunction and exclusion signatures in malignant peripheral nerve sheath tumors reveals susceptibilities to immunotherapy.Journal of neuro-oncology · 2023Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeMalignant peripheral nerve sheath tumors (MPNST) are deadly sarcomas that lack effective therapies. In most MPNSTs, the retinoblastoma (RB1) tumor suppressor is disabled by hyperactivation of cyclin-dependent kinases (CDK), commonly through loss of CDK-inhibitory proteins such as p27(Kip1). RABL6A is an inhibitor of RB1 whose role in MPNSTs is unknown. To gain insight into MPNST development and establish new treatment options, we investigated RABL6A-RB1 signaling and CDK inhibitor-based therapy in MPNSTs. EXPERIMENTAL
designWe examined patient-matched MPNSTs and precursor lesions by RNA sequencing (RNA-Seq) and IHC. Molecular and biological effects of silencing RABL6A and/or p27 in MPNST lines and normal human Schwann cells were determined. Tumor-suppressive effects of CDK inhibitors were measured in MPNST cells and orthotopic tumors.
resultsRABL6A was dramatically upregulated in human MPNSTs compared with precursor lesions, which correlated inversely with p27 levels. Silencing RABL6A caused MPNST cell death and G
conclusionsRABL6A is a new driver of MPNST pathogenesis that acts in part through p27-RB1 inactivation. Our results suggest RB1 targeted therapy with multiple pathway drugs may effectively treat MPNSTs.
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Registered trials
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