ArticleCell death discovery2016
Autophagy mediated by arginine depletion activation of the nutrient sensor GCN2 contributes to interferon-γ-induced malignant transformation of primary bovine mammary epithelial cells.
Article in Cell death discovery, 2016. 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, 48 citations in OpenAlex.
- Amino Acids as Targets for Immunotherapy against Solid Tumors.Cell biochemistry and biophysics · 2026Review
- GCN2 in Cancer: Molecular Mechanisms to Therapeutic Potential.Current cancer drug targets · 2026Review
- Amino acids metabolism: a potential target for cancer treatment.Molecular cancer · 2025Review
- Roughage Sources During Late Gestation and Lactation Alter Metabolism, Immune Function and Rumen Microbiota in Ewes and Their Offsprings.Microorganisms · 2025Article
- Review
- Autophagy: Are Amino Acid Signals Dependent on the mTORC1 Pathway or Independent?Current issues in molecular biology · 2024Review
- Crosstalk between metabolism and cell death in tumorigenesis.Molecular cancer · 2024Review
- Multiple Roles of the Stress Sensor GCN2 in Immune Cells.International journal of molecular sciences · 2023Review
- Untargeted metabolomics reveals alternations in metabolism of bovine mammary epithelial cells upon IFN-γ treatment.BMC veterinary research · 2023Article
- LAP3 contributes to IFN-γ-induced arginine depletion and malignant transformation of bovine mammary epithelial cells.BMC cancer · 2022Article
- Functional Amino Acids and Autophagy: Diverse Signal Transduction and Application.International journal of molecular sciences · 2021Review
- Dietary Valine Ameliorated Gut Health and Accelerated the Development of Nonalcoholic Fatty Liver Disease of Laying Hens.Oxidative medicine and cellular longevity · 2021Article
- IFN-γ Activates the TLR4-CCL5 Signaling Through Reducing Arginine Level, Leading to Enhanced Susceptibility of Bovine Mammary Epithelial Cells to Staphylococcus aureus.Inflammation · 2020Article
- Autophagy elicits a novel and prospect strategy to starve arginine-dependent tumors.Hepatobiliary surgery and nutrition · 2019Article
- GCN2 controls the cellular checkpoint: potential target for regulating inflammation.Cell death discovery · 2018Article
- Aberrant regulation of autophagy in mammalian diseases.Biology letters · 2018Review
- Article
- Diet-driven interferon-γ enhances malignant transformation of primary bovine mammary epithelial cells through nutrient sensor GCN2-activated autophagy.Cell death & disease · 2016Article
- Interferon-γ regulates cell malignant growth via the c-Abl/HDAC2 signaling pathway in mammary epithelial cells.Journal of Zhejiang University. Science. BArticle
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy has been linked to the regulation of both the prevention and progression of cancer. IFN-γ has been shown to induce autophagy in multiple cell lines in vitro. However, whether IFN-γ can induce autophagy and whether autophagy promotes malignant transformation in healthy lactating bovine mammary epithelial cells (BMECs) remain unclear. Here, we provide the first evidence of the correlation between IFN-γ treatment, autophagy and malignant transformation and of the mechanism underlying IFN-γ-induced autophagy and subsequent malignant transformation in primary BMECs. IFN-γ levels were significantly increased in cattle that received normal long-term dietary corn straw (CS) roughage supplementation. In addition, an increase in autophagy was clearly observed in the BMECs from the mammary tissue of cows expressing high levels of IFN-γ. In vitro, autophagy was clearly induced in primary BMECs by IFN-γ within 24 h. This induced autophagy could subsequently promote dramatic primary BMEC transformation. Furthermore, we found that IFN-γ promoted arginine depletion, activated the general control nonderepressible-2 kinase (GCN2) signalling pathway and resulted in an increase in autophagic flux and the amount of autophagy in BMECs. Overall, our findings are the first to demonstrate that arginine depletion and kinase GCN2 expression mediate IFN-γ-induced autophagy that may promote malignant progression and that immunometabolism, autophagy and cancer are strongly correlated. These results suggest new directions and paths for preventing and treating breast cancer in relation to diet.
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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.