ArticleThe Journal of clinical investigation2022
A CGA/EGFR/GATA2 positive feedback circuit confers chemoresistance in gastric cancer.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- The paradox of miR-107 in oncology: dual roles as a tumor suppressor and oncomiR.Cancer gene therapy · 2026Review
- Phosphorylated-EGFR and MMP7 upregulation in gastric cancer: Association with metastasis and poor prognosis.Oncology letters · 2026Article
- JMJD3 upregulates ALOX5 to drive malignancy and concomitant ferroptosis sensitivity in gastric cancer.Cell death & disease · 2025Article
- Article
- Evaluating H2BC9 as a potential diagnostic and prognostic biomarker in head and neck squamous cell carcinoma.European journal of medical research · 2025Article
- Progressive lung fibrosis: reprogramming a genetically vulnerable bronchoalveolar epithelium.The Journal of clinical investigation · 2025Review
- Glycosylation-Related Genes and Prognostic Signatures in Diabetic Nephropathy.International journal of general medicine · 2025Article
- Classical biomarkers and non-coding RNAs associated with diagnosis and treatment in gastric cancer.Oncology research · 2025Review
- Implication of protein post translational modifications in gastric cancer.Frontiers in cell and developmental biology · 2025Review
- The plasticity of epithelial cells and its potential in the induced differentiation of gastric cancer.Cell death discovery · 2024Review
- Mechanism exploration and model construction for small cell transformation in EGFR-mutant lung adenocarcinomas.Signal transduction and targeted therapy · 2024Article
- Amplifying colorectal cancer progression: impact of a PDIA4/SP1 positive feedback loop by circPDIA4 sponging miR-9-5p.Cancer biology & medicine · 2024Article
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Baicalin enhances the chemotherapy sensitivity of oxaliplatin-resistant gastric cancer cells by activating p53-mediated ferroptosis.Scientific reports · 2024Article
- [Screening of differentially expressed genes in gastric cancer based on GEO database and function and pathway enrichment analysis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Transcriptome Analysis Reveals Distinct Patterns Between the Invasive and Noninvasive Pituitary Neuroendocrine Tumors.Journal of the Endocrine Society · 2024Article
- Article
- A novel recombinant ORF7-siRNA delivered by flexible nano-liposomes inhibits varicella zoster virus infection.Cell & bioscience · 2023Article
- Article
- Review
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 3 countries.
Funding
Abstract
De novo and acquired resistance are major impediments to the efficacy of conventional and targeted cancer therapy. In unselected gastric cancer (GC) patients with advanced disease, trials combining chemotherapy and an anti-EGFR monoclonal antibody have been largely unsuccessful. In an effort to identify biomarkers of resistance so as to better select patients for such trials, we screened the secretome of chemotherapy-treated human GC cell lines. We found that levels of CGA, the α-subunit of glycoprotein hormones, were markedly increased in the conditioned media of chemoresistant GC cells, and CGA immunoreactivity was enhanced in GC tissues that progressed on chemotherapy. CGA levels in plasma increased in GC patients who received chemotherapy, and this increase was correlated with reduced responsiveness to chemotherapy and poor survival. Mechanistically, secreted CGA was found to bind to EGFR and activate EGFR signaling, thereby conferring a survival advantage to GC cells. N-glycosylation of CGA at Asn52 and Asn78 is required for its stability, secretion, and interaction with EGFR. GATA2 was found to activate CGA transcription, whose increase, in turn, induced the expression and phosphorylation of GATA2 in an EGFR-dependent manner, forming a positive feedback circuit that was initiated by GATA2 autoregulation upon sublethal exposure to chemotherapy. Based on this circuit, combination strategies involving anti-EGFR therapies or targeting CGA with microRNAs (miR-708-3p and miR-761) restored chemotherapy sensitivity. These findings identify a clinically actionable CGA/EGFR/GATA2 circuit and highlight CGA as a predictive biomarker and therapeutic target in chemoresistant GC.
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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.