ArticleOncogene2020
Oncogenic Smurf1 promotes PTEN wild-type glioblastoma growth by mediating PTEN ubiquitylation.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The trial behind it
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- NSUN4-dependent m5C modification facilitates mitochondrial fission to accelerate diabetic nephropathy process via regulating SMURF1/CAMK1 axis.Clinical and translational medicine · 2026Article
- SMURF1 Regulates CTCF-HOXA10 Axis and Promotes Tumor Progression in Nasopharyngeal Carcinoma.Cancer science · 2026Article
- AMOTL2 inhibits lymph node metastasis in gastric cancer by suppressing TGF-β/Smad signaling and is destabilized by the E3 ubiquitin ligase SMURF1.International journal of biological sciences · 2026Article
- PSMC5 Orchestrates an Immunosuppressive Niche and Metastasis in Colorectal Cancer via SMURF1-Mediated K11-Linked Ubiquitination of METTL14.International journal of biological sciences · 2026Article
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Gal3-CaN-Smurf1 Complex Sequestrates FLCN-FNIPs to Facilitate TFEB Activation in Response to Endomembrane Damage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Transitioning from molecular methods to therapeutic methods: An in‑depth analysis of glioblastoma (Review).Oncology reports · 2025Review
- Overexpression of miR‑424‑5p reduces cisplatin resistance by downregulating SMURF1 in gastric cancer.Oncology letters · 2025Article
- Navigating the Molecular Signaling: Deciphering Cancer Stem Cell Self-Renewal Pathways.International journal of molecular and cellular medicine · 2025Review
- Emerging Insights into the PI3K/AKT/mTOR Signaling Pathway and Non-Coding RNA-mediated Drug Resistance in Glioblastoma.Current molecular medicine · 2025Review
- Advancements in colorectal cancer research: Unveiling the cellular and molecular mechanisms of neddylation (Review).International journal of oncology · 2024Review
- SMURF1 controls the PPP3/calcineurin complex and TFEB at a regulatory node for lysosomal biogenesis.Autophagy · 2024Article
- SMURF1 attenuates endoplasmic reticulum stress by promoting the degradation of KEAP1 to activate NRF2 antioxidant pathway.Cell death & disease · 2023Article
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- Enhanced liquidity of p62 droplets mediated by Smurf1 links Nrf2 activation and autophagy.Cell & bioscience · 2023Article
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- Functional roles of E3 ubiquitin ligases in prostate cancer.Journal of molecular medicine (Berlin, Germany) · 2022Review
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- ESCCAL-1 promotes cell-cycle progression by interacting with and stabilizing galectin-1 in esophageal squamous cell carcinoma.NPJ precision oncology · 2022Article
- Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PI3K/Akt/mTOR signaling pathway activity is highly elevated in glioblastoma (GBM). Although rapamycin is known to inhibit this pathway, GBM patients are resistant to rapamycin monotherapy. This may be related to mutations of tumor suppressor phosphatase and tensin homolog (PTEN). Here, we show that higher expression of E3 ligase Smad ubiquitylation regulatory factor 1 (Smurf1) in GBM is correlated with poor prognosis. Smurf1 promotes cell growth and colony formation by accelerating cell cycle and aberrant signaling pathways. In addition, we show that Smurf1 ubiquitylates and degrades PTEN. We further demonstrate that the oncogenic role of Smurf1 is dependent on PTEN. Upregulated Smurf1 impairs PTEN activity, leading to consistent activation of PI3K/Akt/mTOR signaling pathway; and depletion of Smurf1 dramatically inhibits cell proliferation and tumor growth. Moreover, loss of Smurf1 abolishes the aberrant regulation of PTEN, causing negative feedback on PI3K/Akt/mTOR signaling pathway, and thus leading to rescue of tumor sensitivity to rapamycin in an orthotopic GBM model. Taken together, we show that Smurf1 promotes tumor progression via PTEN, and combined treatment of Smurf1 knockdown with mammalian target of rapamycin (mTOR) inhibition reduces tumor progression. These results identify a unique role of Smurf1 in mTOR inhibitor resistance and provide a strong rationale for combined therapy targeting GBM.
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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.