ArticleCancer letters2021
Palmitic acid negatively regulates tumor suppressor PTEN through T366 phosphorylation and protein degradation.
Article in Cancer letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 40 citations in OpenAlex.
- High-fat intake during lactation ameliorates cardiac fatty acid metabolic disorders and dysfunction in mouse offspring undergoing prenatal poly (I:C) stimulation.Acta pharmacologica Sinica · 2025Article
- Targeting the immunoproteasome in hypothalamic neurons as a novel therapeutic strategy for high-fat diet-induced obesity and metabolic dysregulation.Journal of neuroinflammation · 2024Article
- WTAP/IGF2BP3 mediated m6A modification of the EGR1/PTEN axis regulates the malignant phenotypes of endometrial cancer stem cells.Journal of experimental & clinical cancer research : CR · 2024Article
- Palmitic Acid Exerts Anti-Tumorigenic Activities by Modulating Cellular Stress and Lipid Droplet Formation in Endometrial Cancer.Biomolecules · 2024Article
- Tumorigenesis of basal muscle invasive bladder cancer was mediated by PTEN protein degradation resulting from SNHG1 upregulation.Journal of experimental & clinical cancer research : CR · 2024Article
- Oleic Acid Exhibits Anti-Proliferative and Anti-Invasive Activities via the PTEN/AKT/mTOR Pathway in Endometrial Cancer.Cancers · 2023Article
- Regulatory roles of ACSL5 in the anti-tumor function of palmitic acid (C16:0) <em>via</em> the ERK signaling pathway.European journal of histochemistry : EJH · 2023Article
- Exposure to dietary fatty acids oleic and palmitic acid alters structure and mechanotransduction of intestinal cells in vitro.Archives of toxicology · 2023Article
- Discovering Potential Anti-Oral Squamous Cell Carcinoma Mechanisms from Kochiae Fructus Using Network-Based Pharmacology Analysis and Experimental Validation.Life (Basel, Switzerland) · 2023Article
- Caprylic Acid (FFA C8:0) promotes the progression of prostate cancer by up-regulating G protein-coupled receptor 84/ Krüppel-like factor 7.BMC cancer · 2023Article
- UBR5 targets tumor suppressor CDC73 proteolytically to promote aggressive breast cancer.Cell death & disease · 2022Article
- Metabolic network-based identification of plasma markers for non-small cell lung cancer.Analytical and bioanalytical chemistry · 2021Article
- Quantitative proteomics characterization of cancer biomarkers and treatment.Molecular therapy oncolytics · 2021Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Chronic elevated free fatty (FFA) levels are linked to metabolic disorders and tumorigenesis. However, the molecular mechanism by which FFAs induce cancer remains poorly understood. Here, we show that the tumor suppressor PTEN protein levels were decreased in high fat diet (HFD) fed mice. As palmitic acid (PA, C16:0) showed a significant increase in the HFD fed mice, we further investigated its role in PTEN down regulation. Our studies revealed that exposure of cells to high doses of PA induced mTOR/S6K-mediated phosphorylation of PTEN at T366. The phosphorylation subsequently enhanced the interaction of PTEN with the E3 ubiquitin ligase WW domain-containing protein 2 (WWP2), which promoted polyubiquitination of PTEN and protein degradation. Consistent with PTEN degradation, exposure of cells to increased concentrations of PA also promoted PTEN-mediated AKT activation and cell proliferation. Significantly, a higher level of S6K activation, PTEN T366 phosphorylation, and AKT activation were also observed in the livers of the HFD fed mice. These results provide a molecular mechanism by which a HFD and elevated PA regulate cell proliferation through inactivation of tumor suppressor PTEN.
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