ArticleNature communications2018
Nuclear Smad6 promotes gliomagenesis by negatively regulating PIAS3-mediated STAT3 inhibition.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Clinicopathological and Prognostic Roles of STAT3 and Its Phosphorylation in Glioma.Disease markers · 2020Pooled it
- EIF3B is associated with mBMC cancer · 2026Article
- TRIM25 promotes glioblastoma progression by stabilizing HIF-1α expression in normoxia through K11/K29 polyubiquitination.Cell death & disease · 2026Article
- Dysregulation of post-translational modifications in glioma: advances in pathological mechanisms and clinical targeting strategies.Journal of translational medicine · 2026Review
- Integrating multiomics to elucidate the role of chromatin remodeling in glioma and the antitumor mechanisms and therapeutic potential of targeting LMNA.Frontiers in immunology · 2026Article
- Unique gene patterns lead to distinct functional phenotypes and chemosensitivity profiles among subclones obtained from a single glioblastoma cell line.Acta biochimica et biophysica Sinica · 2025Article
- Hantaan virus glycoprotein Gc induces NEDD4-dependent PTEN ubiquitination and degradation to escape the restriction of autophagosomes and facilitate viral propagation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- STAT signaling pathways in immune cells and their associated mechanisms in cancer pathogenesis.BioImpacts : BI · 2025Review
- Smad1 Promotes Tumorigenicity and Chemoresistance of Glioblastoma by Sequestering p300 From p53.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- A review on potential heterocycles for the treatment of glioblastoma targeting receptor tyrosine kinases.Oncology research · 2024Review
- PIAS family in cancer: from basic mechanisms to clinical applications.Frontiers in oncology · 2024Review
- The SUMOylation and ubiquitination crosstalk in cancer.Journal of cancer research and clinical oncology · 2023Review
- Acetylation halts missense mutant p53 aggregation and rescues tumor suppression in non-small cell lung cancers.iScience · 2023Article
- Global research trends in immunotherapy for glioma: a comprehensive visualization and bibliometric analysis.Frontiers in endocrinology · 2023Article
- Characterization of EGFR-reprogrammable temozolomide-resistant cells in a model of glioblastoma.Cell death discovery · 2022Article
- SHF Acts as a Novel Tumor Suppressor in Glioblastoma Multiforme by Disrupting STAT3 Dimerization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- The positive regulatory loop of TCF4N/p65 promotes glioblastoma tumourigenesis and chemosensitivity.Clinical and translational medicine · 2022Article
- STAT3-mediated osteogenesis and osteoclastogenesis in osteoporosis.Cell communication and signaling : CCS · 2022Review
- Cancer-Associated Dysregulation of Sumo Regulators: Proteases and Ligases.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To date, the molecular mechanism underlying constitutive signal transducer and activator of transcription 3 (STAT3) activation in gliomas is largely unclear. In this study, we report that Smad6 is overexpressed in nuclei of glioma cells, which correlates with poor patient survival and regulates STAT3 activity via negatively regulating the Protein Inhibitors of Activated STAT3 (PIAS3). Mechanically, Smad6 interacts directly with PIAS3, and this interaction is mediated through the Mad homology 2 (MH2) domain of Smad6 and the Ring domain of PIAS3. Smad6 recruits Smurf1 to facilitate PIAS3 ubiquitination and degradation, which also depends on the MH2 domain and the PY motif of Smad6. Consequently, Smad6 reduces PIAS3-mediated STAT3 inhibition and promotes glioma cell growth and stem-like cell initiation. Moreover, the Smad6 MH2 transducible protein restores PIAS3 expression and subsequently reduces gliomagenesis. Collectively, we conclude that nuclear-Smad6 enhances glioma development by inducing PIAS3 degradation and subsequent STAT3 activity upregulation.
Indexed as
Identifiers
What 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.