ArticleOncogene2018
MEKK2 and MEKK3 suppress Hedgehog pathway-dependent medulloblastoma by inhibiting GLI1 function.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Paediatric therapeutic development workshop on medulloblastoma.British journal of cancer · 2026Review
- Ashwagandha (Withania somnifera) targets liver cancer stem cells via inhibiting Hedgehog signaling pathway in hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Article
- Structural basis for MEKK2 dimerization and substrate recognition.Nature communications · 2025Article
- Oncogenic B-Raf proto-oncogene, serine/threonine kinase-mediated hedgehog signalling in the pathogenesis and targeted therapy of melanoma.World journal of clinical oncology · 2025Review
- Phosphorylation of human glioma-associated oncogene 1 on Ser937 regulates Sonic Hedgehog signaling in medulloblastoma.Nature communications · 2024Article
- Sonic hedgehog signaling: Alternative splicing and pathogenic role in medulloblastoma.Genes & diseases · 2023Review
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
- GANT61 exerts anticancer cell and anticancer stem cell capacity in colorectal cancer by blocking the Wnt/β‑catenin and Notch signalling pathways.Oncology reports · 2022Article
- The Functional Role of Long Non-Coding RNAs in Melanoma.Cancers · 2021Review
- MTOR promotes basal cell carcinoma growth through atypical PKC.Experimental dermatology · 2021Article
- WW45 inhibits breast cancer cell proliferation by the Hedgehog signaling pathway.American journal of translational research · 2021Article
- CircPUM1 promotes hepatocellular carcinoma progression through the miR-1208/MAP3K2 axis.Journal of cellular and molecular medicine · 2021Article
- Identification of the Roles of a Stemness Index Based on mRNA Expression in the Prognosis and Metabolic Reprograming of Pancreatic Ductal Adenocarcinoma.Frontiers in oncology · 2021Article
- Long-Pentraxin 3 Affects Primary Cilium in Zebrafish Embryo and Cancer Cells via the FGF System.Cancers · 2020Article
- GLI3: a mediator of genetic diseases, development and cancer.Cell communication and signaling : CCS · 2020Review
- Hedgehog signaling promotes sorafenib resistance in hepatocellular carcinoma patient-derived organoids.Journal of experimental & clinical cancer research : CR · 2020Article
- The Similar Effects of miR-512-3p and miR-519a-2-5p on the Promotion of Hepatocellular Carcinoma: Different Tunes Sung With Equal Skill.Frontiers in oncology · 2020Article
- Crosstalk between SHH and FGFR Signaling Pathways Controls Tissue Invasion in Medulloblastoma.Cancers · 2019Article
- Silencing of the MEKK2/MEKK3 Pathway Protects against Spinal Cord Injury via the Hedgehog Pathway and the JNK Pathway.Molecular therapy. Nucleic acids · 2019Article
- Overexpression of MAP3K3 promotes tumour growth through activation of the NF-κB signalling pathway in ovarian carcinoma.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hedgehog (Hh) pathway plays a pivotal role in diverse aspects of development and postnatal physiology. Perturbation of Hh signaling and activation of GLI1 (glioma-associated oncogene 1), a dedicated transcription factor for Hh pathway, are highly associated with several cancers, such as medulloblastoma and basal cell carcinoma. Dynamic and precise control of GLI1 activity is thus important to ensure proper homeostasis and tumorigenesis. Here we show that MEKK2 (MAP3K2) and MEKK3 (MAP3K3) inhibit GLI1 transcriptional activity and oncogenic function through phosphorylation on multiple Ser/Thr sites of GLI1, which reduces GLI1 protein stability, DNA-binding ability, and increases the association of GLI1 with SUFU. Interestingly, MEKK2 and MEKK3 are responsible for FGF2-mediated inhibition on Hh signaling. Moreover, expression of MEKK2 and MEKK3 inhibits medulloblastoma cell proliferation and negatively correlates with Hh pathway activity in medulloblastoma clinical samples. Together, these findings reveal a novel noncanonical GLI1 regulation and provide a potential therapeutic target for the treatment of cancers with aberrant Hh pathway activation, such as medulloblastoma.
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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.