ArticleJournal of experimental & clinical cancer research : CR2018
GLI2 promotes cell proliferation and migration through transcriptional activation of ARHGEF16 in human glioma cells.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 66 citations in OpenAlex.
- Unraveling lncRNA diversity at a single cell resolution and in a spatial context across different cancer types.Nature methods · 2026Article
- Characterization of quiescent subpopulations and proliferative compartments in glioblastoma.bioRxiv : the preprint server for biology · 2025Article
- Nutritional ketosis modulates the methylation of cancer-related genes in patients with obesity and in breast cancer cells.Journal of physiology and biochemistry · 2025Article
- Phosphorylation of Ephexin4 at Ser-41 contributes to chromosome alignment via RhoG activation in cell division.The Journal of biological chemistry · 2025Article
- Tissue Mechanics and Hedgehog Signaling Crosstalk as a Key Epithelial-Stromal Interplay in Cancer Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Hedgehog ligand and receptor cooperatively regulate EGFR stability and activity in non-small cell lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Pharmacological agents targeting drug-tolerant persister cells in cancer.Pharmacological research · 2024Review
- Intergenomic signatures of coevolution between Tasmanian devils and an infectious cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Ephexin3/ARHGEF5 Together with Cell Migration Signaling Partners within the Tumor Microenvironment Define Prognostic Transcriptional Signatures in Multiple Cancer Types.International journal of molecular sciences · 2023Article
- Liquid biopsy: creating opportunities in brain space.British journal of cancer · 2023Review
- Profound DNA methylomic differences between single- and multi-fraction alpha irradiations of lung fibroblasts.Clinical epigenetics · 2023Article
- Combined ARHGEF6 and Tumor Mutational Burden may serve as a potential biomarker for immunotherapy of lung adenocarcinoma.Heliyon · 2023Article
- ARL13B promotes angiogenesis and glioma growth by activating VEGFA-VEGFR2 signaling.Neuro-oncology · 2023Article
- ARHGEF3 regulates the stability of ACLY to promote the proliferation of lung cancer.Cell death & disease · 2022Article
- CircPDSS1 promotes the proliferation, invasion, migration, and EMT of breast cancer cell via regulating miR-320c/CKAP5 axis.Cancer cell international · 2022Article
- Article
- Cepharanthine hydrochloride inhibits the Wnt/β‑catenin/Hedgehog signaling axis in liver cancer.Oncology reports · 2022Article
- Aberrant expression of the extracellular matrix component Biglycan regulated by Hedgehog signalling promotes colorectal cancer cell proliferation.Acta biochimica et biophysica Sinica · 2022Article
- Research Progress on the Regulation Mechanism of Key Signal Pathways Affecting the Prognosis of Glioma.Frontiers in molecular neuroscience · 2022Review
- AURKA gene polymorphisms and central nervous system tumor susceptibility in Chinese children.Discover oncology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe Hedgehog (Hh) signaling pathway plays critical roles in modulating embryogenesis and maintaining tissue homeostasis, with glioma-associated oncogene (GLI) transcription factors being the main mediators. Aberrant activation of this pathway is associated with various human malignancies including glioblastoma, although the mechanistic details are not well understood.
methodsWe performed a microarray analysis of genes that are differentially expressed in glioblastoma U87 cells overexpressing GLI2A, the active form of GLI2, relative to the control cells. Chromatin immunoprecipitation and dual-luciferase assays were used to determine whether Rho guanine nucleotide exchange factor 16 (ARHGEF16) is a downstream target of GLI2. Then, transwell migration, EdU and soft-agar colony formation assays were employed to test effects of ARHGEF16 on glioma cancer cell migration and proliferation, and the effects of GLI2/ARHGEF16 signaling on tumor growth were examined in vivo. Finally, we performed yeast two-hybrid assay, Co-IP and GST-pull down to identify factors that mediate effects of ARHGEF16.
resultsWe found that ARHGEF16 mRNA level was upregulated in U87 cells overexpressing GLI2A relative to control cells. GLI2 binds to the ARHGEF16 promoter and activates gene transcription. Glioma cells U87 and U118 overexpressing ARHGEF16 showed enhanced migration and proliferation relative to the control cells, while knockdown of ARHGEF16 in H4 cells led to decreased cell proliferation compared to the control H4 cells. In contrast to the promoting effect of GLI2A overexpression on glioma xenograft growth, both GLI2 inhibition and ARHGEF16 knockdown retarded tumor growth. Cytoskeleton-associated protein 5 (CKAP5) was identified as an interaction protein of ARHGEF16, which is important for the stimulatory effects of ARHGEF16 on glioma cell migration and proliferation.
conclusionsThese results suggest that therapeutic strategies targeting the GLI2/ARHGEF16/CKAP5 signaling axis could inhibit glioma progression and recurrence.
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