ArticleSignal transduction and targeted therapy2023
RBM4 dictates ESCC cell fate switch from cellular senescence to glutamine-addiction survival through inhibiting LKB1-AMPK-axis.
Article in Signal transduction and targeted therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
- piR‑164552 promotes malignant progression in head and neck squamous cell carcinoma via the RBM4/EIF4E2 signaling axis: Insights from multi‑omics and functional analyses.International journal of oncology · 2026Article
- RBM4 Promotes Nasopharyngeal Carcinoma Growth and Metastasis by Stabilizing HOXB13 mRNA.Cell biochemistry and biophysics · 2026Article
- Correction: RBM4 dictates ESCC cell fate switch from cellular senescence to glutamine-addiction survival through inhibiting LKB1-AMPK-axis.Signal transduction and targeted therapy · 2026Article
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- The translation landscape of ovarian clear cell carcinoma indicates that RBM4 plays a pro-oncogenic role in tumor progression.Oncogene · 2026Article
- Identification of a myosin 1B-binding aptamer for fluorescence imaging and targeted therapy of esophageal squamous cell carcinoma.Materials today. Bio · 2026Article
- Glutaminase 1 in Vascular Disease: Linking Metabolic Reprogramming to Atherosclerosis Progression and Stability.Journal of cardiovascular translational research · 2026Review
- PF protects retinal pigment epithelial cells from oxidative injury by enhancing mitophagy through a CUL3-dependent AMPK/ULK1 pathway.Archives of pharmacal research · 2026Article
- Targeted Clearance of Senescent Endothelium by GPNMB-Specific CAR-T Cells.Journal of immunology research · 2026Article
- RBM3-associated germline variants and their functional role in gastric cancer susceptibility and progression.Frontiers in oncology · 2026Article
- Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.Frontiers in cell and developmental biology · 2026Review
- Beyond Glucose and Lipids: The Pivotal Role of Amino Acid Reprogramming in Shaping the Tumor Microenvironment and Guiding the Development of Novel Therapeutics.International journal of medical sciences · 2026Review
- Lactylation-driven KRT19 promotes non-small cell lung cancer progression by suppressing cellular senescence.Journal of experimental & clinical cancer research : CR · 2025Article
- Glutamine: a new strategy for targeted metabolic therapy in the tumor microenvironment.Cell death discovery · 2025Review
- Hsa_circ_0075451 promotes NSCLC proliferation, metastasis, and glycolysis through interaction with the RNA-binding protein RBM4.Discover oncology · 2025Article
- Triclabendazole inhibits PKM2 nuclear localization and glycolysis by enhancing HDAC6-mediated deacetylation in lung cancer.Journal of translational medicine · 2025Article
- The bidirectional interplay between RNA processing and mechanotransduction.Cell reports · 2025Review
- Natural Killer Cell-Mediated Antitumor Immunity: Molecular Mechanisms and Clinical Applications.MedComm · 2025Review
- Senescence of dental pulp stem cells: phenotypes, underlying mechanisms and regulatory molecules.Human cell · 2025Review
- Machine learning developed LKB1-AMPK signaling related signature for prognosis and drug sensitivity in hepatocellular carcinoma.Scientific reports · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular senescence provides a protective barrier against tumorigenesis in precancerous or normal tissues upon distinct stressors. However, the detailed mechanisms by which tumor cells evade premature senescence to malignant progression remain largely elusive. Here we reported that RBM4 adversely impacted cellular senescence to favor glutamine-dependent survival of esophageal squamous cell carcinoma (ESCC) cells by dictating the activity of LKB1, a critical governor of cancer metabolism. The level of RBM4 was specifically elevated in ESCC compared to normal tissues, and RBM4 overexpression promoted the malignant phenotype. RBM4 contributed to overcome H-RAS- or doxorubicin-induced senescence, while its depletion caused P27-dependent senescence and proliferation arrest by activating LKB1-AMPK-mTOR cascade. Mechanistically, RBM4 competitively bound LKB1 to disrupt the LKB1/STRAD/MO25 heterotrimeric complex, subsequently recruiting the E3 ligase TRIM26 to LKB1, promoting LKB1 ubiquitination and degradation in nucleus. Therefore, such molecular process leads to bypassing senescence and sustaining cell proliferation through the activation of glutamine metabolism. Clinically, the ESCC patients with high RBM4 and low LKB1 have significantly worse overall survival than those with low RBM4 and high LKB1. The RBM4 high/LKB1 low expression confers increased sensitivity of ESCC cells to glutaminase inhibitor CB-839, providing a novel insight into mechanisms underlying the glutamine-dependency to improve the efficacy of glutamine inhibitors in ESCC therapeutics.
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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.