ArticleCell death and differentiation2021
Constitutive GLI1 expression in chondrosarcoma is regulated by major vault protein via mTOR/S6K1 signaling cascade.
Article in Cell death and differentiation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- LEM-Domain-Containing Inner Nuclear Membrane Proteins: Emerging Regulators of Intranuclear Signaling.International journal of molecular sciences · 2026Review
- Chondrosarcoma organoids reveal SHH pathway activation driven by PTCH1 and BCOR alterations.Scientific reports · 2025Article
- Saikosaponin b1 Attenuates Liver Fibrosis by Blocking STAT3/Gli1 Interaction and Inducing Gli1 Degradation.Exploration (Beijing, China) · 2025Article
- SIRT7-Mediated MVP Desuccinylation Facilitates Tongue Squamous Cell Carcinoma Progression by Activating JAK2/STAT3 Pathway.Cell biology international · 2025Article
- Vault Particles in Cancer Progression, Multidrug Resistance, and Drug Delivery: Current Insights and Future Applications.International journal of molecular sciences · 2025Review
- The fungal microbiota modulate neonatal oxygen-induced lung injury.Microbiome · 2025Article
- NLRP3 promotes the proliferation and metastasis of colorectal cancer by regulating the S6K1-GLI1 signaling pathway.Journal of Cancer · 2025Article
- KDELR1 regulates chondrosarcoma drug resistance and malignant behavior through Intergrin-Hippo-YAP1 axis.Cell death & disease · 2024Article
- Hedgehog pathway and cancer: A new area (Review).Oncology reports · 2024Review
- Estrogen counteracts age-related decline in beige adipogenesis through the NAMPT-regulated ER stress response.Nature aging · 2024Article
- Gli1-mediated tumor cell-derived bFGF promotes tumor angiogenesis and pericyte coverage in non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Hedgehog pathway in sarcoma: from preclinical mechanism to clinical application.Journal of cancer research and clinical oncology · 2023Review
- Article
- Targeting the hedgehog pathway in MET mutation cancers and its effects on cells associated with cancer development.Cell communication and signaling : CCS · 2023Review
- Article
- Development of an osteosarcoma model with MYCN amplification and TP53 mutation in hiPS cell-derived neural crest cells.Cancer science · 2023Article
- Chondrosarcoma Resistance to Radiation Therapy: Origins and Potential Therapeutic Solutions.Cancers · 2023Review
- ABT-737 suppresses aberrant Hedgehog pathway and overcomes resistance to smoothened antagonists by blocking Gli.Medical oncology (Northwood, London, England) · 2022Article
- Nuclear import of PTPN18 inhibits breast cancer metastasis mediated by MVP and importin β2.Cell death & disease · 2022Article
- Inhibition of mTOR/S6K1/Gli1 signaling alleviates morphine-induced thermal hyperalgesia and tolerance.Molecular painArticle
Corrections and comments
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
Hedgehog signaling plays a pivotal role in embryonic pattern formation and diverse aspects of the postnatal biological process. Perturbation of the hedgehog pathway and overexpression of GLI1, a downstream transcription factor in the hedgehog pathway, are highly relevant to several malignancies including chondrosarcoma (CS). We previously found that knocking down expression of GLI1 attenuates the disrupted Indian hedgehog (IHH) signal pathway and suppresses cell survival in human CS cells. However, the underlying mechanisms regulating the expression of GLI1 are still unknown. Here, we demonstrated the implication of GLI1 in SMO-independent pathways in CS cells. A GLI1 binding protein, major vault protein (MVP), was identified using the affinity purification method. MVP promoted the nuclear transport and stabilization of GLI1 by compromising the binding affinity of GLI1 with suppressor of fused homolog (SUFU) and increased GLI1 expression via mTOR/S6K1 signaling cascade. Functionally, knockdown of MVP suppressed cell growth and induced apoptosis. Simultaneous inhibition of MVP and GLI1 strongly inhibits the growth of CS in vitro and in vivo. Moreover, IHC results showed that MVP, GLI1, and P-p70S6K1 were highly expressed and positively correlated with each other in 71 human CS tissues. Overall, our findings revealed a novel regulating mechanism for HH-independent GLI1 expression and provide a rationale for combination therapy in patients with advanced CS.
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