ArticleOncogenesis2015
A positive feedback loop between Gli1 and tyrosine kinase Hck amplifies shh signaling activities in medulloblastoma.
Article in Oncogenesis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Helicobacter pylori-induced aberrant methylation of ID4 mediated by DNMT3B drives gastric cancer progression via DEC1-SHH signaling pathway.Cell death & disease · 2025Article
- Positioning of negative feedback loops within immune signaling pathways influences gene expression noise.bioRxiv : the preprint server for biology · 2025Article
- P4HA2 hydroxylates SUFU to regulate the paracrine Hedgehog signaling and promote B-cell lymphoma progression.Leukemia · 2024Article
- Phosphorylation of human glioma-associated oncogene 1 on Ser937 regulates Sonic Hedgehog signaling in medulloblastoma.Nature communications · 2024Article
- Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review.Cellular and molecular life sciences : CMLS · 2022Review
- STAT3 is required for Smo-dependent signaling and mediates Smo-targeted treatment resistance and tumorigenesis in Shh medulloblastoma.Molecular oncology · 2022Article
- Balancing the length of the distal tip by septins is key for stability and signalling function of primary cilia.The EMBO journal · 2022Article
- Targeting H3K27me3 demethylase to inhibit Shh signaling and cholesterol metabolism in medulloblastoma growth.Frontiers in oncology · 2022Article
- A highly multiplexed quantitative phosphosite assay for biology and preclinical studies.Molecular systems biology · 2021Article
- Hedgehog Signaling and Truncated GLI1 in Cancer.Cells · 2020Review
- The stem cell-associated transcription co-factor, ZNF521, interacts with GLI1 and GLI2 and enhances the activity of the Sonic hedgehog pathway.Cell death & disease · 2019Article
- Review
- MEP50/PRMT5-mediated methylation activates GLI1 in Hedgehog signalling through inhibition of ubiquitination by the ITCH/NUMB complex.Communications biology · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sonic hedgehog (Shh) signaling is critical during normal development, and the abnormal activation of the Shh pathway is involved in many human cancers. As a target gene of the Shh pathway and as a transcription activator downstream of Shh signaling, Gli1 autoregulates and increases Shh signaling output. Gli1 is one of the key oncogenic factors in Shh-induced tumors such as medulloblastoma. Gli1 is posttranslationally modified, but the nature of the active form of Gli1 was unclear. Here we identified a Src family kinase Hck as a novel activator of Gli1. In Shh-responsive NIH3T3 cells, Hck interacts with Gli1 and phosphorylates multiple tyrosine residues in Gli1. Gli1-mediated target gene activation was significantly enhanced by Hck with both kinase activity-dependent and -independent mechanisms. We provide evidence showing that Hck disrupts the interaction between Gli1 and its inhibitor Sufu. In both NIH3T3 cells and cerebellum granule neuron precursors, the Hck gene is also a direct target of Gli1. Therefore, Gli1 and Hck form a positive feedback loop that amplifies Shh signaling transcription outcomes. In Shh-induced medulloblastoma, Hck is highly expressed and Gli1 is tyrosine phosphorylated, which may enhance the tumorigenic effects of the Gli1 oncogene. RNAi-mediated inhibition of Hck expression significantly repressed medulloblastoma cell growth. In summary, a novel positive feedback loop contributes to maximal Gli1 oncogenic activities in Shh-induced tumors 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.