ArticleCell death & disease2020
Prohibitin, STAT3 and SH2D4A physically and functionally interact in tumor cell mitochondria.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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
21 citing papers in PubMed, 32 citations in OpenAlex.
- QAL333's antitumor activity and predictive modeling: integrated transcriptomic-bioinformatic analysis reveals selective cytotoxicity and sensitivity determinants.Scientific reports · 2026Article
- A mitochondrial regulatory network of ferroptosis defense in HPV-positive cervical cancer: therapeutic implications of the mitoSTAT3-DHODH axis.Frontiers in pharmacology · 2026Review
- Deep learning analysis of urine-derived stem cell mitochondrial morphology as a non-invasive Alzheimer's disease biomarker.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Comprehensive Genetic Map of Muscle Lipidome Reveals Novel Insights Into Flavor Variation in Ruminant Meat.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- DIRAS1 Drives Oxaliplatin Resistance in Colorectal Cancer via PHB1-Mediated Mitochondrial Homeostasis.Biology · 2025Article
- The E3 Ubiquitin Ligase ARIH1 Facilitates Colorectal Cancer Progression by Promoting Oxidative Phosphorylation via the Mitochondrial Translocation of K63-Linked Ubiquitinated PHB1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Meis transcription factors regulate cardiac conduction system development and adult function.Cardiovascular research · 2025Article
- Macrophage PTP1B regulates mitochondrial dynamics via the JAK2/STAT3-OPA1 axis and activates the cGAS/STING signaling pathway.Frontiers in immunology · 2025Article
- The ubiquitin-specific protease 21 is critical for cancer cell mitochondrial function and regulates proliferation and migration.The Journal of biological chemistry · 2024Article
- UBXN1 promotes liver tumorigenesis by regulating mitochondrial homeostasis.Journal of translational medicine · 2024Article
- Loss of prohibitin 2 in Schwann cells dysregulates key transcription factors controlling developmental myelination.bioRxiv : the preprint server for biology · 2024Article
- Pyruvate kinase M2 sustains cardiac mitochondrial integrity in septic cardiomyopathy by regulating PHB2-dependent mitochondrial biogenesis.International journal of medical sciences · 2024Article
- Article
- Analysis of Radiation Toxicity in Mammalian Cells Stably Transduced with MitochondrialInternational journal of molecular sciences · 2023Article
- LPLUNC1 reduces glycolysis in nasopharyngeal carcinoma cells through the PHB1-p53/c-Myc axis.Cancer science · 2023Article
- System analysis based on the migration- and invasion-related gene sets identifies the infiltration-related genes of glioma.Frontiers in oncology · 2023Article
- Discovery of potent STAT3 inhibitors using structure-based virtual screening, molecular dynamic simulation, and biological evaluation.Frontiers in oncology · 2023Article
- STAT1 and STAT3 Exhibit a Crosstalk and Are Associated with Increased Inflammation in Hepatocellular Carcinoma.Cancers · 2022Article
- Mitochondrial STAT3 exacerbates LPS-induced sepsis by driving CPT1a-mediated fatty acid oxidation.Theranostics · 2022Article
- Obesity and Fatty Acids Promote Mitochondrial Translocation of STAT3 Through ROS-Dependent Mechanisms.Frontiers in aging · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chromosome 8p is frequently deleted in various cancer entities and has been shown to correlate with poor patient survival. SH2D4A is located on chromosome 8p and prevents the nuclear translocation of the pro-tumorigenic transcription factor STAT3. Here, we investigated the interaction of SH2D4A and STAT3 to shed light on the non-canonical functions of STAT3 in cooperation with the tumor suppressor SH2D4A. Using an immunoprecipitation-mass spectrometry (IP-MS) approach, we identified the mitochondrial scaffold proteins prohibitin 1 (PHB1) and prohibitin 2 (PHB2) among other proteins to potentially bind to SH2D4A. Co-immunoprecipitation and proximity ligation assays confirmed direct interactions of STAT3, PHB1, and SH2D4A in situ and in vitro. In addition, cell fractionation and immunofluorescence staining revealed co-localization of these proteins with mitochondria. These interactions were selectively interrupted by the small molecule and PHB ligand FL3. Furthermore, FL3 led to a reduction of STAT3 protein levels, STAT3 transcriptional activity, and HIF1α protein stabilization upon dimethyloxalylglycine (DMOG) treatment. Besides, mitochondrial fusion and fission markers, L-OPA1, Mfn1, and FIS1, were dysregulated upon FL3 treatment. This dysregulated morphology was accompanied by significant reduction of mitochondrial respiration, thus, FL3 significantly diminished mitochondrial respirational capacity. In contrast, SH2D4A knockout increased mitochondrial respiration, whereas FL3 reversed the effect of SH2D4A knockout. The here described results indicate that the interaction of SH2D4A and PHB1 is involved in the mitochondrial function and integrity. The demonstrated interaction with STAT3, accompanied by its reduction of transcriptional activity, further suggests that SH2D4A is linking STAT3 to its mitochondrial functions, and inhibition of PHB-interaction may have therapeutic effects in tumor cells with STAT3 activation.
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.