ArticleCell death & disease2022
TRIM46 activates AKT/HK2 signaling by modifying PHLPP2 ubiquitylation to promote glycolysis and chemoresistance of lung cancer cells.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 61 citations in OpenAlex.
- LAMB3 drives gastric cancer progression through SAMD4A-mediated degradation of PHLPP2 mRNA leading to sustained PI3K-Akt activation.British journal of cancer · 2026Article
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Article
- TRIM46 deficiency‑induced DNA damage enhances the sensitivity of cisplatin in non‑small cell lung cancer by regulating the Akt signaling pathway.Oncology reports · 2026Article
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- Anlotinib enhances the sensitivity to docetaxel in lung cancer through inhibiting DDR1-mediated glycolytic pathway.International journal of biological sciences · 2026Article
- TRIM14 Regulation of Copper Homeostasis and Cuproptosis: A New Strategy to Overcome Chemoresistance in Glioblastoma.Biomedicines · 2025Article
- Demethoxycurcumin suppresses HK2-mediated glycolysis by targeting PTEN/Akt signaling.Cancer gene therapy · 2025Article
- ATP6V0D2 drives triple-negative breast cancer progression and inhibits cisplatin sensitivity by promoting PHLPP2 lysosomal degradation.iScience · 2025Article
- Targeting Skp2 by Tanshinone IIA overcomes chemoresistance in colorectal cancer.Cell biology and toxicology · 2025Article
- Hypomethylation-Enhanced F-Box Protein 32 Promotes Hepatocellular Carcinogenesis via Ubiquitin-Mediated PHLPP2 Degradation.MedComm · 2025Article
- AFF4 promotes tumor progression and cisplatin resistance by modulating the PTEN/PI3K/AKT/mTOR axis to accelerate glycolysis in lung adenocarcinoma.Cell & bioscience · 2025Article
- TRIM65 regulates glucose metabolic reprogramming to promote glioma cell proliferation via ubiquitination and degradation of AMPK.NPJ precision oncology · 2025Article
- Targeting PI3K signaling in Lung Cancer: advances, challenges and therapeutic opportunities.Journal of translational medicine · 2025Review
- Article
- LncRNA CCAT1 knockdown suppresses tongue squamous cell carcinoma progression by inhibiting the ubiquitination of PHLPP2.Molecular and cellular biochemistry · 2025Article
- DDP Induced Cytotoxicity through miR-215-5p/COL5A1/FSTL1 Axis to Regulate Autophagy in Lung Adenocarcinoma Cells.Current pharmaceutical biotechnology · 2025Article
- Hexokinase 2 promotes tumor development and progression.American journal of cancer research · 2025Review
- The Role of HK2 in Tumorigenesis and Development: Potential for Targeted Therapy with Natural Products.International journal of medical sciences · 2025Review
- Multifaceted role ofMedComm · 2024Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The incidence of lung cancer is increasing worldwide. Although great progress in lung cancer treatment has been made, the clinical outcome is still unsatisfactory. Tripartite motif (TRIM)-containing proteins has been shown to be closely related to tumor progression. However, the function of TRIM46 in lung cancer is largely unknown. Here, TRIM46 amplification was found in lung adenocarcinoma (LUAD) tissues and TRIM46 amplification was significantly associated with a poor survival rate. Overexpression of wild type TRIM46 increased the proliferation of LUAD cells and glycolysis, promoted xenografts growth, and enhanced cisplatin (DDP) resistance of LUAD cells via increased ubiquitination of pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2) and upregulation of p-AKT. In contrast, overexpression of RING-mutant TRIM46 did not show any effects, suggesting the function of TRIM46 was dependent on the E3 ligase activity. Furthermore, we found that TRIM46 promoted LUAD cell proliferation and DDP resistance by enhancing glycolysis. PHLPP2 overexpression reversed the effects of TRIM46 overexpression. Amplification of TRIM46 also promoted LUAD growth and enhanced its DDP resistance in a patient-derived xenograft (PDX) model. In conclusion, our data highlight the importance of TRIM46/PHLPP2/AKT signaling in lung cancer and provide new insights into therapeutic strategies for lung cancer.
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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.