ArticleStem cells (Dayton, Ohio)2013
MELK-dependent FOXM1 phosphorylation is essential for proliferation of glioma stem cells.
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 134 papers, 1 of them a synthesis that pooled it.
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Who cites it
134 citing papers in PubMed, 1 synthesis or guideline pooled it, 202 citations in OpenAlex.
- Genetics of breast cancer bone metastasis: a sequential multistep pattern.Clinical & experimental metastasis · 2014Pooled it
- Vernodalin andBiomedicines · 2026Article
- Discovery of the MELK-Nucleostemin Axis in Glioblastoma: Implications for p53 Regulation and Tumor Progression.Journal of microbiology and biotechnology · 2026Article
- Maternal Embryonic Leucine Zipper Kinase (Biology · 2026Review
- Prognostic significance of the MELK/TMPO-AS1/hsa-let-7b-5p network in lung adenocarcinoma.Frontiers in oncology · 2026Article
- The role of MELK in cancer: mechanisms and therapeutic options.Frontiers in oncology · 2026Review
- Characterizing the Effects of Protein Glycosylation Perturbation on Phosphorylation Signaling.bioRxiv : the preprint server for biology · 2025Article
- Predictive molecular biomarkers of radiosensitivity in adult glioma: a narrative review.BMC cancer · 2025Review
- Review
- Up-Regulation of MELK Promotes Cell Growth and Invasion by Accelerating G1/S Transition and Indicates Poor Prognosis in Lung Adenocarcinoma.Molecular biotechnology · 2025Article
- MELK as a Mediator of Stemness and Metastasis in Aggressive Subtypes of Breast Cancer.International journal of molecular sciences · 2025Article
- 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
- CPI203, a BET inhibitor, down-regulates a consistent set of DNA synthesis genes across a wide array of glioblastoma lines.PloS one · 2025Article
- Upregulation of MELK promotes chemoresistance and induces macrophage M2 polarization via CSF-1/JAK2/STAT3 pathway in gastric cancer.Cancer cell international · 2024Article
- DDX56 promotes EMT and cancer stemness via MELK-FOXM1 axis in hepatocellular carcinoma.iScience · 2024Article
- The Emerging Role of Ubiquitin-Specific Protease 36 (USP36) in Cancer and Beyond.Biomolecules · 2024Review
- Emerging Roles and Mechanisms of RNA Modifications in Neurodegenerative Diseases and Glioma.Cells · 2024Review
- Forkhead box transcription factors (FOXOs and FOXM1) in glioma: from molecular mechanisms to therapeutics.Cancer cell international · 2023Review
- 5-Aminolevulinic acid increases boronophenylalanine uptake into glioma stem cells and may sensitize malignant glioma to boron neutron capture therapy.Scientific reports · 2023Article
74 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Glioblastoma multiforme (GBM) is a life-threatening brain tumor. Accumulating evidence suggests that eradication of glioma stem-like cells (GSCs) in GBM is essential to achieve cure. The transcription factor FOXM1 has recently gained attention as a master regulator of mitotic progression of cancer cells in various organs. Here, we demonstrate that FOXM1 forms a protein complex with the mitotic kinase MELK in GSCs, leading to phosphorylation and activation of FOXM1 in a MELK kinase-dependent manner. This MELK-dependent activation of FOXM1 results in a subsequent increase in mitotic regulatory genes in GSCs. MELK-driven FOXM1 activation is regulated by the binding and subsequent trans-phosphorylation of FOXM1 by another kinase PLK1. Using mouse neural progenitor cells (NPCs), we found that transgenic expression of FOXM1 enhances, while siRNA-mediated gene silencing diminishes neurosphere formation, suggesting that FOXM1 is required for NPC growth. During tumorigenesis, FOXM1 expression sequentially increases as cells progress from NPCs, to pretumorigenic progenitors and GSCs. The antibiotic Siomycin A disrupts MELK-mediated FOXM1 signaling with a greater sensitivity in GSC compared to neural stem cell. Treatment with the first-line chemotherapy agent for GBM, Temozolomide, paradoxically enriches for both FOXM1 (+) and MELK (+) cells in GBM cells, and addition of Siomycin A to Temozolomide treatment in mice harboring GSC-derived intracranial tumors enhances the effects of the latter. Collectively, our data indicate that FOXM1 signaling through its direct interaction with MELK regulates key mitotic genes in GSCs in a PLK1-dependent manner and thus, this protein complex is a potential therapeutic target for 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.