Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor and bi-functional lipid and protein phosphatase. We report that the metabolic regulator pyruvate dehydrogenase kinase1 (PDHK1) is a synthetic-essential gene in PTEN-deficient cancer and normal cells. The PTEN protein phosphatase dephosphorylates nuclear factor κB (NF-κB)-activating protein (NKAP) and limits NFκB activation to suppress expression of PDHK1, a NF-κB target gene. Loss of the PTEN protein phosphatase upregulates PDHK1 to induce aerobic glycolysis and PDHK1 cellular dependence. PTEN-deficient human tumors harbor increased PDHK1, a biomarker of decreased patient survival. This study uncovers a PTEN-regulated signaling pathway and reveals PDHK1 as a potential target in PTEN-deficient cancers.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728083 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2019.07.063 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Hydrogen Sulfide Promotes TAM-M1 Polarization through Activating IRE-1α Pathway via GRP78 S-Sulfhydrylation to against Breast Cancer.
Adv Sci (Weinh)
January 2025
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, China.
Hydrogen sulfide (HS)-mediated protein S-sulfhydration has been shown to play critical roles in several diseases. Tumor-associated macrophages (TAMs) are the predominant population of immune cells present within solid tumor tissues, and they function to restrict antitumor immunity. However, no previous study has investigated the role of protein S-sulfhydration in TAM reprogramming in breast cancer (BC).
View Article and Find Full Text PDFInhibition of HDAC6 elicits anticancer effects on head and neck cancer cells through Sp1/SOD3/MKP1 signaling axis to downregulate ERK phosphorylation.
Cell Signal
January 2025
Institute of Medical Science, Ajou University School of Medicine, Suwon, Gyeonggi 16499, Republic of Korea; Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Gyeonggi 16499, Republic of Korea. Electronic address:
Oxidative stress caused by reactive oxygen species (ROS) and superoxides is linked to various cancer-related biological events. Extracellular superoxide dismutase (SOD3), an antioxidant enzyme that removes superoxides, contributes to redox homeostasis and has the potential to regulate tumorigenesis. Histone deacetylase 6 (HDAC6), a major HDAC isoform responsible for mediating the deacetylation of non-histone protein substrates, also plays a role in cancer progression.
View Article and Find Full Text PDFNatural Products From Plants Targeting Leptin Resistance for the Future Development of Anti-Obesity Agents.
Phytother Res
January 2025
Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
Obesity is a serious health threat, which has affected 16% of adults globally in 2022 and shows a trend toward youthfulness. Leptin, as a regulator of body weight, can suppress appetite and promote energy expenditure, making it potential in obesity treatment. Nevertheless, with the progress of relevant research, it is worth noting that monotherapy with leptin is not an effective strategy since most obese individuals are hyperleptinemic and resistant to leptin, where high levels of leptin fail to exert its weight-loss effects.
View Article and Find Full Text PDFRepressing cytokine storm-like response in macrophages by targeting the eIF2α-integrated stress response pathway.
Int Immunopharmacol
January 2025
Department of Geriatric Medicine, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong Province, China. Electronic address:
Cytokine storm is a life-threatening systemic hyper-inflammatory state caused by different etiologies, in which the bulk production of pro-inflammatory cytokines from activated macrophages has a central role. Integrated stress response (ISR) comprises several protective signaling pathways, leading to phosphorylation of eukaryotic initiation factor 2α (eIF2α) and repression of protein translation. Emerging evidence suggests that ISR induction may elicit anti-inflammatory effects.
View Article and Find Full Text PDFFunctional differences between rodent and human PD-1 linked to evolutionary divergence.
Sci Immunol
January 2025
Department of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.
Mechanistic understanding of the inhibitory immunoreceptor PD-1 is largely based on mouse models, but human and mouse PD-1 share only 59.6% amino acid identity. Here, we found that human PD-1 is more inhibitory than mouse PD-1, owing to stronger interactions with the ligands PD-L1 and PD-L2 and more efficient recruitment of the effector phosphatase Shp2.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!