Glioblastoma are highly aggressive brain tumors with poor prognosis. While various dysregulation of signaling pathways in gliomas have been described, the identification of biomarkers and therapy targets remains an important task for novel diagnostic and therapeutic approaches. Here we described that the Suppressor of fused (also known as Sufu) is significantly down-regulated in high-grade gliomas, correlating with a poor prognosis. We demonstrated that ectopic expression of Sufu inhibited cell proliferation, invasion and vasculogenic mimicry. In addition, overexpression of Sufu reduced Gli reporter gene transcription activity and prevented Gli1 nuclear accumulation, whereas knockdown of Sufu reversed these effects. Furthermore, overexpressed Sufu sensitized glioblastoma to Temozolomide and Cyclopamine. Thus, Sufu is potential tumor suppressor and therapeutic target in glioblastoma.
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http://dx.doi.org/10.18632/oncotarget.2585 | DOI Listing |
Elife
January 2025
Department of Neurology, Weill Institute for Neuroscience, University of California San Francisco, San Francisco, United States.
Mutations in Sonic Hedgehog (SHH) signaling pathway genes, for example, (SUFU), drive granule neuron precursors (GNP) to form medulloblastomas (MB). However, how different molecular lesions in the Shh pathway drive transformation is frequently unclear, and mutations in the cerebellum seem distinct. In this study, we show that fibroblast growth factor 5 (FGF5) signaling is integral for many infantile MB cases and that expression is uniquely upregulated in infantile MB tumors.
View Article and Find Full Text PDFCell Death Dis
December 2024
Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Frankfurt, Germany.
The concept of Targeted Protein Degradation (TPD) has been introduced as an attractive alternative to the development of classical inhibitors. TPD can extend the range of proteins that can be pharmacologically targeted beyond the classical targets for small molecule inhibitors, as a binding pocket is required but its occupancy does not need to lead to inhibition. The method is based on either small molecules that simultaneously bind to a protein of interest and to a cellular E3 ligase and bring them in close proximity (molecular glue) or a bi-functional molecule synthesized from the chemical linkage of a target protein-specific small molecule and one that binds to an E3 ligase (Proteolysis Targeting Chimeras (PROTAC)).
View Article and Find Full Text PDFCell Mol Life Sci
December 2024
Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128, Palermo, Italy.
Methylation of cytosine in CpG dinucleotides is an epigenetic modification carried out by DNA-methyltransferases (DNMTs) that contributes to chromatin condensation and structure and, thus, to gene transcription regulation and chromosome stability. DNMT1 maintains the DNA methylation pattern of the genome at each cell cycle by copying it to the newly synthesized DNA strand during the S-phase. DNMT1 pharmacological inhibition as well as genetic knockout and knockdown, leads to passive DNA methylation loss.
View Article and Find Full Text PDFJ Cell Biol
February 2025
Institute of Molecular Biology, Mainz, Germany.
Functional genomics with libraries of knockout alleles is limited to non-essential genes and convoluted by the potential accumulation of suppressor mutations in knockout backgrounds, which can lead to erroneous functional annotations. To address these limitations, we constructed genome-wide libraries of conditional alleles based on the auxin-inducible degron (AID) system for inducible degradation of AID-tagged proteins in the budding yeast Saccharomyces cerevisiae. First, we determined that N-terminal tagging is at least twice as likely to inadvertently impair protein function across the proteome.
View Article and Find Full Text PDFZhen Ci Yan Jiu
December 2024
College of Acupuncture-moxibustion and Tuina, Anhui University of Chinese Medicine, Hefei 230038, China.
Objectives: To explore whether electroacupuncture(EA) can increase the expression of suppressor of cytokine signaling (SOCS)3 by affecting the expression of miR-19b-3p, inhibiting the continuous activation of janus kinase (JAK)1 /signal transducer and activator of transcription (STAT)3 signaling pathway, and improve pulmonary inflammation in chronic obstructive pulmonary disease (COPD) mice.
Methods: Forty mice were randomly divided into normal, COPD model, COPD+EA, and COPD+miR-19b-3p agomir (agomir)+EA groups. The COPD model was simulated by cigarette smoke exposure for 1 h, twice a day for 3 months.
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