ArticleiScience2021
Smurf1 silencing restores PTEN expression that ameliorates progression of human glioblastoma and sensitizes tumor cells to mTORC1/C2 inhibitor Torin1.
Article in iScience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Specific inhibition of NLRP3 inflammasome by a Smurf1 inhibitorOpen medicine (Warsaw, Poland) · 2026Article
- Gal3-CaN-Smurf1 Complex Sequestrates FLCN-FNIPs to Facilitate TFEB Activation in Response to Endomembrane Damage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A Perspective on Therapeutic Targeting Against Ubiquitin Ligases to Stabilize Tumor Suppressor Proteins.Cancers · 2025Review
- SMURF1 controls the PPP3/calcineurin complex and TFEB at a regulatory node for lysosomal biogenesis.Autophagy · 2024Article
- Smurf1 Modulates Smad Signaling Pathway in Fibrotic Cataract Formation.Investigative ophthalmology & visual science · 2024Article
- Enhanced liquidity of p62 droplets mediated by Smurf1 links Nrf2 activation and autophagy.Cell & bioscience · 2023Article
- Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amplification of ubiquitin E3 ligase Smurf1 promotes degradation of PTEN leading to hyperactivation of the Akt/mTORC1 pathway. However, inhibitors of this pathway have not hitherto yielded promising results in clinical studies because of strong drug resistance. Here, we investigated Smurf1 expression in various glioblastoma (GB) cell lines and patient tissues. The therapeutic efficacy of Smurf1 silencing and Torin1 treatment was assessed in GB cells and orthotopic mouse model. We found Smurf1 loss elevates PTEN levels that interrupt the epidermal growth factor receptor pathway activity. Cotreatment with Smurf1 silencing and mTORC1/C2 inhibitor Torin1 remarkably decreased phosphorylation of Akt, and mTORC1 downstream targets 4EBP1 and S6K resulting in synergistic inhibitory effects. Smurf1 knockdown in orthotopic GB mouse model impaired tumor growth and enhanced cytotoxicity of Torin1. Together, these findings suggest a rational combination of Smurf1 inhibition and Torin1 as a promising new avenue to circumvent PI3K/Akt pathway-driven tumor progression and drug resistance.
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Registered trials
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