ArticleOncogenesis2018
IKKβ activates p53 to promote cancer cell adaptation to glutamine deprivation.
Article in Oncogenesis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
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
23 citing papers in PubMed, 28 citations in OpenAlex.
- Fueling Prostate Cancer: The Central Role of Glutamine/Glutamate Metabolic Reprogramming.Asian Pacific journal of cancer prevention : APJCP · 2025Review
- A hormetic response model for glutamine stress in cancer.Trends in cancer · 2025Review
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Advances in multifunctional metal-organic framework (MOF)-based nanoplatforms for cancer starvation therapy.Expert reviews in molecular medicine · 2024Review
- Targeting cellular adaptive responses to glutaminolysis perturbation for cancer therapy.Molecules and cells · 2024Review
- Prolyl hydroxylase 2 inhibits glycolytic activity in colorectal cancer via the NF‑κB signaling pathway.International journal of oncology · 2024Article
- Combination L-Glutamine with Gemcitabine and Nab-Paclitaxel in Treatment-Naïve Advanced Pancreatic Cancer: The Phase I GlutaPanc Study Protocol.Biomedicines · 2023Article
- Targeting glutamine metabolism as a therapeutic strategy for cancer.Experimental & molecular medicine · 2023Review
- The Four Homeostasis Knights: In Balance upon Post-Translational Modifications.International journal of molecular sciences · 2022Review
- Current status of cancer starvation therapy.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022Review
- IKKActa pharmaceutica Sinica. B · 2022Article
- Review
- Deciphering the PTM codes of the tumor suppressor p53.Journal of molecular cell biology · 2022Review
- Protein of a thousand faces: The tumor-suppressive and oncogenic responses of p53.Frontiers in molecular biosciences · 2022Review
- Enhanced triacylglycerol catabolism by carboxylesterase 1 promotes aggressive colorectal carcinoma.The Journal of clinical investigation · 2021Article
- Article
- Immunosuppression Induced by Glutamine Deprivation OccursFrontiers in molecular biosciences · 2021Article
- Astragalus polysaccharides attenuate pulmonary fibrosis by inhibiting the epithelial-mesenchymal transition and NF-κB pathway activation.International journal of molecular medicine · 2020Article
- A systematic approach to decipher crosstalk in the p53 signaling pathway using single cell dynamics.PLoS computational biology · 2020Article
- NEnvironmental pollution (Barking, Essex : 1987) · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
One of the hallmarks of cancer is the ability to reprogram cellular metabolism to increase the uptake of necessary nutrients such as glucose and glutamine. Driven by oncogenes, cancer cells have increased glutamine uptake to support their highly proliferative nature. However, as cancer cells continue to replicate and grow, they lose access to vascular tissues and deplete local supply of nutrients and oxygen. We previously showed that many tumor cells situate in a low glutamine microenvironment in vivo, yet the mechanisms of how they are able to adapt to this metabolic stress are still not fully understood. Here, we report that IκB-kinase β (IKKβ) is needed to promote survival and its activation is accompanied by phosphorylation of the metabolic sensor, p53, in response to glutamine deprivation. Knockdown of IKKβ decreases the level of wild-type and mutant p53 phosphorylation and its transcriptional activity, indicating a novel relationship between IKKβ and p53 in mediating cancer cell survival in response to glutamine withdrawal. Phosphopeptide mass spectrometry analysis further reveals that IKKβ phosphorylates p53 on Ser392 to facilitate its activation upon glutamine deprivation, independent of the NF-κB pathway. The results of this study offer an insight into the metabolic reprogramming in cancer cells that is dependent on a previously unidentified IKKβ-p53 signaling axis in response to glutamine depletion. More importantly, this study highlights a new therapeutic strategy for cancer treatment and advances our understanding of adaptive mechanisms that could lead to resistance to current glutamine targeting therapies.
Identifiers
What OpenQuestion holds
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.