ArticleLaboratory investigation; a journal of technical methods and pathology2019
O-GlcNAcylation of GLI transcription factors in hyperglycemic conditions augments Hedgehog activity.
Article in Laboratory investigation; a journal of technical methods and pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Glutamine stress promotes metastatic potential via hexosamine biosynthetic pathway activity in KRAS/STK11-mutant lung adenocarcinoma.Research square · 2026Article
- OGT-Mediated O-GlcNAcylation Stabilizes c-Myc Activity and Promotes Chemoresistance in Triple-Negative Breast Cancer.The breast journal · 2026Article
- The complex interplay between diabetes mellitus and pancreatic carcinogenesis: deciphering multifactorial mechanisms and identifying emerging therapeutic vulnerabilities.Cell & bioscience · 2025Review
- O‑GlcNAcylation as an emerging molecular target for cholangiocarcinoma therapy (Review).Oncology reports · 2025Review
- Probing the biological efficacy and mechanistic pathways of natural compounds in breast cancer therapy via the Hedgehog signaling pathway.Journal of pharmaceutical analysis · 2025Review
- O-GlcNAcylation in Gli1International journal of molecular sciences · 2025Article
- O-GlcNAcylation-related genes mediate tumor microenvironment characteristics and prediction of immunotherapy response in gastric cancer.Acta biochimica et biophysica Sinica · 2024Article
- O-GlcNAcylation: roles and potential therapeutic target for bone pathophysiology.Cell communication and signaling : CCS · 2024Review
- Article
- Role of O-GlcNAcylation on cancer stem cells: Connecting nutrient sensing to cell plasticity.Advances in cancer research · 2023Review
- O-GlcNAcylation promotes cerebellum development and medulloblastoma oncogenesis via SHH signaling.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Glucose Increases STAT3 Activation, Promoting Sustained XRCC1 Expression and Increasing DNA Repair.International journal of molecular sciences · 2022Article
- Arginine glycosylation regulates UDP-GlcNAc biosynthesis in Salmonella enterica.Scientific reports · 2022Article
- Normalizing glucose levels reconfigures the mammary tumor immune and metabolic microenvironment and decreases metastatic seeding.Cancer letters · 2021Article
- Role ofPhysiological reviews · 2021Review
- O-GlcNAcylation and O-GlcNAc Cycling Regulate Gene Transcription: Emerging Roles in Cancer.Cancers · 2021Review
- Hedgehog Signaling and Truncated GLI1 in Cancer.Cells · 2020Review
- Catalytic deficiency of O-GlcNAc transferase leads to X-linked intellectual disability.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) promotes tumor cell survival, proliferation, epigenetic changes, angiogenesis, invasion, and metastasis. Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway. In elevated glucose conditions, we determined that the Hedgehog pathway transcription factors, GLI1 and GLI2, are modified by O-GlcNAcylation. This modification functionally enhanced their transcriptional activity. The activity of GLI was enhanced when O-GlcNAcase was inhibited, while inhibiting O-GlcNAc transferase caused a decrease in GLI activity. The metabolic impact of hyperglycemic conditions impinges on maintaining PKM2 in the less active state that facilitates the availability of glycolytic intermediates for biosynthetic pathways. Interestingly, under elevated glucose conditions, PKM2 directly influenced GLI activity. Specifically, abrogating PKM2 expression caused a significant decline in GLI activity and expression of drug resistance proteins. Cumulatively, our results suggest that elevated glucose conditions upregulate chemoresistance through elevated transcriptional activity of the Hedgehog/GLI pathway. Interfering in O-GlcNAcylation of the GLI transcription factors may be a novel target in controlling cancer progression and drug resistance of breast cancer.
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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.