ArticleCell death & disease2021
GLI1 reduces drug sensitivity by regulating cell cycle through PI3K/AKT/GSK3/CDK pathway in acute myeloid leukemia.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 45 citations in OpenAlex.
- CREB1 and GSK3 Isoforms as Potential Adaptive Signaling Nodes in PI3K/Akt/mTOR Inhibitor Treated Philadelphia Chromosome-Positive B-ALL.International journal of molecular sciences · 2026Article
- MNAT1 in gastrointestinal cancers: mechanistic insights and therapeutic strategies-a narrative review.Journal of gastrointestinal oncology · 2026Review
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- SUMOylation activates ECHS1 for adaptive catabolism in lung cancer.Cell death & disease · 2026Article
- HHIP's dynamic role in epithelial wound healing reveals a potential mechanism of COPD susceptibility.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- SNX1 inhibits human ovarian cancer progression via regulation of the cell cycle, apoptosis and migration.Molecular & cellular oncology · 2026Article
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- Integrated metabolomic and transcriptomic analysis identifies adipogenic differentiation of mesenchymal stem cells as a driver of chemoresistance in acute myeloid leukemia.Journal of experimental & clinical cancer research : CR · 2025Article
- Marine-Derived Enteromorpha prolifera Polysaccharides Suppress Castration-Resistant Prostate Cancer via Akt1 Inhibition.The journal of gene medicine · 2025Article
- Hedgehog pathway, cell cycle, and primary cilium.Cell death discovery · 2025Review
- Mitochondrial fission regulator 2 promotes cell proliferation, migration and invasion in hepatocellular carcinoma through regulating PI3K/AKT signaling pathway.Cell division · 2025Article
- Plasma Protein Binding, Biostability, Metabolite Profiling, and CYP450 Phenotype of TPB15 Across Different Species: A Novel Smoothened Inhibitor for TNBC Therapy.Pharmaceutics · 2025Article
- Mechanistic insights into PROS1 inhibition of bladder cancer progression and angiogenesis via the AKT/GSK3β/β-catenin pathway.Scientific reports · 2025Article
- FGFC1 overcomes Ara-C resistance in acute myeloid leukemia by inducing apoptosis and pyroptosis.Frontiers in pharmacology · 2025Article
- GANT61 surmounts drug resistance of ADR by upregulating lysosome activities and reducing BCL2 expression in HL-60/ADR cells.Cancer cell international · 2024Article
- HHIP's Dynamic Role in Epithelial Wound Healing Reveals a Potential Mechanism of COPD Susceptibility.bioRxiv : the preprint server for biology · 2024Article
- Hedgehog pathway and cancer: A new area (Review).Oncology reports · 2024Review
- Titanium Dioxide Nanoparticles Induce Cell Cycle Arrest and Apoptosis through Inhibiting PI3K/AKT/mTOR Pathway in Spermatogonia.Biological trace element research · 2024Article
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Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) is a hematological malignancy with high incidence and recurrence rates. Gene expression profiling has revealed that transcriptional overexpression of glioma-associated oncogene 1 (GLI1), a vital gene in the Hedgehog (Hh) signaling pathway, occurs in poor-prognosis AML, and high levels of phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1) and AKT3 predict shorter overall survival in AML patients. In this study, we discovered that GLI1 overexpression promotes cell proliferation and reduces chemotherapy sensitivity in AML cells while knocking down GLI1 has the opposite effect. Moreover, GLI1 promoted cell cycle progression and led to elevated protein levels of cyclins and cyclin-dependent kinases (CDKs) in AML cells. By luciferase assays and co-immunoprecipitation, we demonstrated that the PI3K/AKT pathway is directly activated by GLI1. GLI1 overexpression significantly accelerates tumor growth and upregulated p-AKT, CDK4, and cyclinD3 in vivo. Notably, the GLI1 inhibitor GANT61 and the CDK4/6 inhibitor PD 0332991 had synergistic effects in promoting Ara-c sensitivity in AML cell lines and patient samples. Collectively, our data demonstrate that GLI1 reduces drug sensitivity by regulating cell cycle through the PI3K/AKT/GSK3/CDK pathway, providing a new perspective for involving GLI1 and CDK4/6 inhibitors in relapsed/refractory (RR) patient treatment.
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