ArticleNature communications2020
TRIM21 and PHLDA3 negatively regulate the crosstalk between the PI3K/AKT pathway and PPP metabolism.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 153 citations in OpenAlex.
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- The PI3K/AKT signaling networks in cancer glucose metabolism: mechanisms and therapeutic implications.Translational oncology · 2026Review
- Novel curcumin derivative DMC-GF suppresses glioblastoma growth by targeting MAPK1 and TRIM21 to modulates STAT3/AKT phosphorylation.Discover oncology · 2026Article
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- Effects ofBiology · 2026Article
- SUMOylation-stabilized G6PD orchestrates metabolic rewiring for oxidative stress survival and chemoresistance in HCC via a PKCδ-phosphorylation trigger.Cell death and differentiation · 2026Article
- Correlation analysis of blood metabolites and periventricular leukomalacia in preterm infants two weeks postnatally.Scientific reports · 2026Article
- TRIM21-mediated ubiquitination of PARP1 regulated by the PI3K/AKT-STAT5A axis suppresses small cell lung cancer.Nature communications · 2026Article
- CircNOLC1/KRT16 promotes colorectal cancer invasion and migration via c-met nuclear translocation and reprogramming of the oxidative pentose phosphate pathway.The Journal of biological chemistry · 2026Article
- Identification of the E3 ligase TRIM21 as a crucial regulator of STAT1 in metabolic dysfunction-associated steatohepatitis.Cell communication and signaling : CCS · 2026Article
- TRIM21 and OTUD6A orchestrate AKT K27-linked atypical ubiquitination to modulate cancer chemoresistance.Nature structural & molecular biology · 2026Article
- Mechanistic Research on the Crosstalk Between Macrophage Polarization and Energy Metabolic Reprogramming in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Review
- The mechanism of the PI3K-AKT-mTOR signaling pathway in renal cell carcinoma: current developments and future prospects.Frontiers in oncology · 2026Review
- p300: expanding beyond acetylation to mastermind lactylation-dependent tumorigenesis.Frontiers in cell and developmental biology · 2026Review
- Article
- Amylin inhibits gastric cancer progression by targeting CCN1 and affecting the PI3K/AKT signalling pathway.Annals of medicine · 2025Article
- Non-canonical roles of Keap1/Nrf2 in regulating quiescence and early activation in adult muscle stem cells.Nature communications · 2025Article
- STXBP6 regulates growth, metastasis and lipid metabolism of ovarian cancer cells via the PI3K/AKT signaling pathway.Medical oncology (Northwood, London, England) · 2025Article
- IRGM Inhibits the AKT/mTOR Signaling Pathway by Interacting with TRIM21 to Alleviate Sepsis-Induced Acute Lung Injury.Inflammation · 2025Article
- RIOK1 phase separation restricts PTEN translation via stress granules activating tumor growth in hepatocellular carcinoma.Nature cancer · 2025Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PI3K/AKT signaling is known to regulate cancer metabolism, but whether metabolic feedback regulates the PI3K/AKT pathway is unclear. Here, we demonstrate the important reciprocal crosstalk between the PI3K/AKT signal and pentose phosphate pathway (PPP) branching metabolic pathways. PI3K/AKT activation stabilizes G6PD, the rate-limiting enzyme of the PPP, by inhibiting the newly identified E3 ligase TIRM21 and promotes the PPP. PPP metabolites, in turn, reinforce AKT activation and further promote cancer metabolic reprogramming by blocking the expression of the AKT inhibitor PHLDA3. Knockout of TRIM21 or PHLDA3 promotes crosstalk and cell proliferation. Importantly, PTEN null human cancer cells and in vivo murine models are sensitive to anti-PPP treatments, suggesting the importance of the PPP in maintaining AKT activation even in the presence of a constitutively activated PI3K pathway. Our study suggests that blockade of this reciprocal crosstalk mechanism may have a therapeutic benefit for cancers with PTEN loss or PI3K/AKT activation.
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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.