ArticleStem cells (Dayton, Ohio)2013
Tumor-specific activation of the C-JUN/MELK pathway regulates glioma stem cell growth in a p53-dependent manner.
Article in Stem cells (Dayton, Ohio), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 2 of them syntheses that pooled it.
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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.
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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.
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Who cites it
78 citing papers in PubMed, 2 syntheses or guidelines pooled it, 108 citations in OpenAlex.
- Expression and Prognostic Significance of p53 in Glioma Patients: A Meta-analysis.Neurochemical research · 2016Pooled it
- Genetics of breast cancer bone metastasis: a sequential multistep pattern.Clinical & experimental metastasis · 2014Pooled it
- Trial
- MELK inhibition disrupts actin cytoskeleton and broadly restricts human coronavirus infections.Nature communications · 2026Article
- Maternal Embryonic Leucine Zipper Kinase (Biology · 2026Review
- The role of MELK in cancer: mechanisms and therapeutic options.Frontiers in oncology · 2026Review
- Targeting MELK in tumor cells and tumor microenvironment: from function and mechanism to therapeutic application.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Maternal Embryonic Leucine Zipper Kinase (MELK) as a Promising Therapeutic Target in Triple Negative Breast Cancer.Anti-cancer agents in medicinal chemistry · 2025Review
- Upregulation of MELK promotes chemoresistance and induces macrophage M2 polarization via CSF-1/JAK2/STAT3 pathway in gastric cancer.Cancer cell international · 2024Article
- Tumor cell-intrinsic MELK enhanced CCL2-dependent immunosuppression to exacerbate hepatocarcinogenesis and confer resistance of HCC to radiotherapy.Molecular cancer · 2024Article
- Kunitz-type protease inhibitor TFPI2 remodels stemness and immunosuppressive tumor microenvironment in glioblastoma.Nature immunology · 2023Article
- Gene Expression Profile of 3D Spheroids in Comparison with 2D Cell Cultures and Tissue Strains of Diffuse High-Grade Gliomas.Bulletin of experimental biology and medicine · 2023Article
- 5-Aminolevulinic acid increases boronophenylalanine uptake into glioma stem cells and may sensitize malignant glioma to boron neutron capture therapy.Scientific reports · 2023Article
- Proteomic analysis reveals microvesicles containing NAMPT as mediators of radioresistance in glioma.Life science alliance · 2023Article
- Homologous repair deficiency-associated genes in invasive breast cancer revealed by WGCNA co-expression network analysis and genetic perturbation similarity analysis.Cell cycle (Georgetown, Tex.) · 2023Article
- The Role of Cellular Prion Protein in Glioma Tumorigenesis Could Be through the Autophagic Mechanisms: A Narrative Review.International journal of molecular sciences · 2023Review
- Tumor treating fields induced senescence on glioblastoma.American journal of cancer research · 2023Article
- MELK predicts poor prognosis and promotes metastasis in esophageal squamous cell carcinoma via activating the NF‑κB pathway.International journal of oncology · 2022Article
- Maternal embryonic leucine zipper kinase serves as a potential prognostic marker and leads to sorafenib chemoresistance modified by miR-142-5p in hepatocellular carcinoma.Molecular biology reports · 2022Article
- Circ_0007031 Silencing Inhibits Cell Proliferation and Induces Cell Apoptosis via Downregulating MELK at a miR-485-3p-Dependent Way in Colorectal Cancer.Biochemical genetics · 2022Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Accumulated evidence suggests that glioma stem cells (GSCs) may contribute to therapy resistance in high-grade glioma (HGG). Although recent studies have shown that the serine/threonine kinase maternal embryonic leucine-zipper kinase (MELK) is abundantly expressed in various cancers, the function and mechanism of MELK remain elusive. Here, we demonstrate that MELK depletion by shRNA diminishes the growth of GSC-derived mouse intracranial tumors in vivo, induces glial fibrillary acidic protein (+) glial differentiation of GSCs leading to decreased malignancy of the resulting tumors, and prolongs survival periods of tumor-bearing mice. Tissue microarray analysis with 91 HGG tumors demonstrates that the proportion of MELK (+) cells is a statistically significant indicator of postsurgical survival periods. Mechanistically, MELK is regulated by the c-Jun NH(2)-terminal kinase (JNK) signaling and forms a complex with the oncoprotein c-JUN in GSCs but not in normal progenitors. MELK silencing induces p53 expression, whereas p53 inhibition induces MELK expression, indicating that MELK and p53 expression are mutually exclusive. Additionally, MELK silencing-mediated GSC apoptosis is partially rescued by both pharmacological p53 inhibition and p53 gene silencing, indicating that MELK action in GSCs is p53 dependent. Furthermore, irradiation of GSCs markedly elevates MELK mRNA and protein expression both in vitro and in vivo. Clinically, recurrent HGG tumors following the failure of radiation and chemotherapy exhibit a statistically significant elevation of MELK protein compared with untreated newly diagnosed HGG tumors. Together, our data indicate that GSCs, but not normal cells, depend on JNK-driven MELK/c-JUN signaling to regulate their survival, maintain GSCs in an immature state, and facilitate tumor radioresistance in a p53-dependent manner.
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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.