ArticleCell reports2022
EGFR-phosphorylated GDH1 harmonizes with RSK2 to drive CREB activation and tumor metastasis in EGFR-activated lung cancer.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Stress-responsive membrane proteins as execution nodes of tumor cell adaptation to microenvironmental stress.Oncogene · 2026Review
- Anoikis-Related Genes Can Accurately Predict the Occurrence of Endometriosis: A Retrospective Cohort Study via Machine Learning Analysis.Biochemical genetics · 2026Article
- GLUD1 supports ovarian cancer progression by counteracting anoikis via ARAF/MEK/ERK signaling.NPJ precision oncology · 2026Article
- Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding.Cancer letters · 2025Review
- Fibronectin 1 Aggravates Colon Cancer Metastasis by Regulating RAP1B Protein Stability Through Akt/CREB Signalling Pathway.Journal of cellular and molecular medicine · 2025Article
- Review
- Integrating machine learning and multi-omics analysis to unveil key programmed cell death patterns and immunotherapy targets in kidney renal clear cell carcinoma.Scientific reports · 2025Article
- cAMP response element-binding protein: A credible cancer drug target.The Journal of pharmacology and experimental therapeutics · 2025Review
- Glutamate dehydrogenase 1-catalytic glutaminolysis feedback activates EGFR/PI3K/AKT pathway and reprograms glioblastoma metabolism.Neuro-oncology · 2025Article
- Targeting RSK2 in Cancer Therapy: A Review of Natural Products.Anti-cancer agents in medicinal chemistry · 2025Review
- Comprehensive analysis of single-cell and bulk RNA sequencing data reveals an EGFR signature for predicting immunotherapy response and prognosis in pan-cancer.Frontiers in immunology · 2025Article
- Hypoxia-anoikis-related genes in LUAD: machine learning and RNA sequencing analysis of immune infiltration and therapy response.American journal of cancer research · 2025Article
- RSK1 and RSK2 as therapeutic targets: an up-to-date snapshot of emerging data.Expert opinion on therapeutic targets · 2024Review
- Glutamate Transport Proteins and Metabolic Enzymes are Poor Prognostic Factors in Invasive Lobular Carcinoma.bioRxiv : the preprint server for biology · 2024Article
- Tumour cell-derived serglycin promotes IL-8 secretion of CAFs in gastric cancer.British journal of cancer · 2024Article
- What enlightenment has the development of lung cancer bone metastasis brought in the last 22 years.World journal of clinical oncology · 2024Article
- A glutamine tug-of-war between cancer and immune cells: recent advances in unraveling the ongoing battle.Journal of experimental & clinical cancer research : CR · 2024Review
- Gefitinib induces anoikis in cervical cancer cells.BMB reports · 2024Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
The cancer metastasis process involves dysregulated oncogenic kinase signaling, but how this orchestrates metabolic networks and signal cascades to promote metastasis is largely unclear. Here we report that inhibition of glutamate dehydrogenase 1 (GDH1) and ribosomal S6 kinase 2 (RSK2) synergistically attenuates cell invasion, anoikis resistance, and immune escape in lung cancer and more evidently in tumors harboring epidermal growth factor receptor (EGFR)-activating or EGFR inhibitor-resistant mutations. Mechanistically, GDH1 is activated by EGFR through phosphorylation at tyrosine 135 and, together with RSK2, enhances the cAMP response element-binding protein (CREB) activity via CaMKIV signaling, thereby promoting metastasis. Co-targeting RSK2 and GDH1 leads to enhanced intratumoral CD8 T cell infiltration. Moreover, GDH1, RSK2, and CREB phosphorylation positively correlate with EGFR mutation and activation in lung cancer patient tumors. Our findings reveal a crosstalk between kinase, metabolic, and transcription machinery in metastasis and offer an alternative combinatorial therapeutic strategy to target metastatic cancers with activated EGFRs that are often EGFR therapy resistant.
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Registered trials
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.