ArticleCell death & disease2017
mTORC2 regulates hedgehog pathway activity by promoting stability to Gli2 protein and its nuclear translocation.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 30 papers.
What it found
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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
30 citing papers in PubMed, 39 citations in OpenAlex.
- Metformin potentiates arsenic disulfide in diffuse large B-cell lymphoma: modulation of BAX/BCL-2 apoptotic pathway and hedgehog pathway.Frontiers in oncology · 2026Article
- Paracrine FGF21 dynamically modulates mTOR signaling to regulate thymus function across the lifespan.Nature aging · 2025Article
- Cross-modal contrastive learning decodes developmental regulatory features through chromatin potential analysis.GigaScience · 2025Article
- CARD9 protein SUMOylation regulates HOXB5 nuclear translocation and Parkin-mediated mitophagy in myocardial I/R injury.Journal of cellular and molecular medicine · 2024Article
- mTORC1 hampers Hedgehog signaling inLife science alliance · 2024Article
- Veratridine, a plant-derived alkaloid, suppresses the hyperactive Rictor-mTORC2 pathway: a new targeted therapy for primary and metastatic colorectal cancer.Research square · 2024Article
- Hedgehog pathway and cancer: A new area (Review).Oncology reports · 2024Review
- The anti-tumor activity of tangeretin in esophageal squamous cell carcinoma by inhibiting GLI2-mediated transcription of GPNMB.PloS one · 2024Article
- Hedgehog pathway in sarcoma: from preclinical mechanism to clinical application.Journal of cancer research and clinical oncology · 2023Review
- Liquid biopsy: creating opportunities in brain space.British journal of cancer · 2023Review
- UBXN2A suppresses the Rictor-mTORC2 signaling pathway, an established tumorigenic pathway in human colorectal cancer.Oncogene · 2023Article
- Glioblastoma Microenvironment and Invasiveness: New Insights and Therapeutic Targets.International journal of molecular sciences · 2023Review
- Maternal hyperglycemia inhibits pulmonary vasculogenesis during mouse fetal lung development by promoting GβL Ubiquitination-dependent mammalian target of Rapamycin assembly.Diabetology & metabolic syndrome · 2023Article
- Hedgehog signaling regulates the development and treatment of glioblastoma.Oncology letters · 2022Review
- Article
- Inhibition of Gli2 suppresses tumorigenicity in glioblastoma stem cells derived from a de novo murine brain cancer model.Cancer gene therapy · 2021Article
- MTOR promotes basal cell carcinoma growth through atypical PKC.Experimental dermatology · 2021Article
- Desialylation of Atg5 by sialidase (Neu2) enhances autophagosome formation to induce anchorage-dependent cell death in ovarian cancer cells.Cell death discovery · 2021Article
- Regulator of cullins-1 (ROC1) negatively regulates the Gli2 regulator SUFU to activate the hedgehog pathway in bladder cancer.Cancer cell international · 2021Article
- Article
Corrections and comments
- Retraction · 2024-05-21Concerns/Issues about Data · Error in Image · Objections by Author(s) · Unreliable Data ·
- Retracted
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
mTORC2 is aberrantly activated in cancer and therefore is considered to be an important therapeutic target. The hedgehog pathway, which is also often hyperactivated, regulates transcription of several genes associated with angiogenesis, metastasis, cellular proliferation and cancer stem cell (CSC) regeneration. However, the contribution of mTORC2 toward hedgehog pathway activity has not been explored yet. Here we have addressed the molecular cross talk between mTORC2 and hedgehog pathway activities in the context of glioblastoma multiforme, a malignant brain tumor using as a model system. We observed that higher mTORC2 activity enhanced the expression of a few hedgehog pathway molecules (Gli1, Gli2 and Ptch1) and amplified its target genes (Cyclin D1, Cyclin D2, Cyclin E, Snail, Slug and VEGF) both in mRNA and protein levels as corroborated by increased metastasis, angiogenesis, cellular proliferation and stem cell regeneration. Inhibition of mTORC2 formation decreased hedgehog pathway activity and attenuated all these above-mentioned events, suggesting their cross talk with each other. Further investigations revealed that mTORC2 inhibited ubiquitination of Gli2 by inactivating GSK3β, and thus it promotes stability to Gli2 and its nuclear translocation. Moreover, enhanced mTORC2 activity led to the increased clonogenic properties and CD133
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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.