ArticleOncogene2015
Hedgehog/GLI and PI3K signaling in the initiation and maintenance of chronic lymphocytic leukemia.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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.
The trial behind it
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
33 citing papers in PubMed, 60 citations in OpenAlex.
- Review
- Alpha-estradiol and (R)-(-)-ibuprofen inhibit gastric cancer progression via GLI1 G-quadruplex.Frontiers in pharmacology · 2025Article
- Interactions between hedgehog signaling pathway and the complex tumor microenvironment in breast cancer: current knowledge and therapeutic promises.Cell communication and signaling : CCS · 2024Review
- The Connection between MiR-122 and Lymphocytes in Patients Receiving Treatment for Chronic Hepatitis B Virus Infection.Microorganisms · 2023Article
- Multiprotein GLI Transcriptional Complexes as Therapeutic Targets in Cancer.Life (Basel, Switzerland) · 2022Review
- The crosstalk between long non-coding RNAs and the hedgehog signaling pathway in cancer.Medical oncology (Northwood, London, England) · 2022Review
- The hedgehog pathway in hematopoiesis and hematological malignancy.Frontiers in oncology · 2022Review
- Hedgehog Suppresses Paclitaxel Sensitivity by Regulating Akt-Mediated Phosphorylation of Bax in EGFR Wild-Type Non-Small Cell Lung Cancer Cells.Frontiers in pharmacology · 2022Article
- HELQ and EGR3 expression correlate with IGHV mutation status and prognosis in chronic lymphocytic leukemia.Journal of translational medicine · 2021Article
- Hedgehog Signaling: Implications in Cancers and Viral Infections.International journal of molecular sciences · 2021Review
- Minibrain-related kinase/dual-specificity tyrosine-regulated kinase 1B implication in stem/cancer stem cells biology.World journal of stem cells · 2020Review
- GLI3: a mediator of genetic diseases, development and cancer.Cell communication and signaling : CCS · 2020Review
- Activation of hedgehog signaling associates with early disease progression in chronic lymphocytic leukemia.Blood · 2019Article
- Review
- Role of Protein Kinases in Hedgehog Pathway Control and Implications for Cancer Therapy.Cancers · 2019Review
- Novel-smoothened inhibitors for therapeutic targeting of naïve and drug-resistant hedgehog pathway-driven cancers.Acta pharmacologica Sinica · 2019Article
- Correlation of Gli1 and HER2 expression in gastric cancer: Identification of novel target.Scientific reports · 2018Article
- Molecular Interactions Between Innate and Adaptive Immune Cells in Chronic Lymphocytic Leukemia and Their Therapeutic Implications.Frontiers in immunology · 2018Review
- Role and inhibition of GLI1 protein in cancer.Lung Cancer (Auckland, N.Z.) · 2018Review
- Emerging Roles of DYRK Kinases in Embryogenesis and Hedgehog Pathway Control.Journal of developmental biology · 2017Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The initiation and maintenance of a malignant phenotype requires complex and synergistic interactions of multiple oncogenic signals. The Hedgehog (HH)/GLI pathway has been implicated in a variety of cancer entities and targeted pathway inhibition is of therapeutic relevance. Signal cross-talk with other cancer pathways including PI3K/AKT modulates HH/GLI signal strength and its oncogenicity. In this study, we addressed the role of HH/GLI and its putative interaction with the PI3K/AKT cascade in the initiation and maintenance of chronic lymphocytic leukemia (CLL). Using transgenic mouse models, we show that B-cell-specific constitutive activation of HH/GLI signaling either at the level of the HH effector and drug target Smoothened or at the level of the GLI transcription factors does not suffice to initiate a CLL-like phenotype characterized by the accumulation of CD5(+) B cells in the lymphatic system and peripheral blood. Furthermore, Hh/Gli activation in Pten-deficient B cells with activated Pi3K/Akt signaling failed to enhance the expansion of leukemic CD5(+) B cells, suggesting that genetic or epigenetic alterations leading to aberrant HH/GLI signaling in B cells do not suffice to elicit a CLL-like phenotype in mice. By contrast, we identify a critical role of GLI and PI3K signaling for the survival of human primary CLL cells. We show that combined targeting of GLI and PI3K/AKT/mTOR signaling can have a synergistic therapeutic effect in cells from a subgroup of CLL patients, thereby providing a basis for the evaluation of future combination therapies targeting HH/GLI and PI3K signaling in this common hematopoietic malignancy.
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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.