ArticleGenes & diseases2023
PD-L1 expression is regulated by ATP-binding of the ERBB3 pseudokinase domain.
Article in Genes & diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 13 citations in OpenAlex.
- Methyltransferase-like 7B promotes M2-like macrophage polarization in lung adenocarcinoma via upregulating human epidermal growth factor receptor 3 expression and secretion.Oncology letters · 2026Article
- Construction of an ATP hydrolysis-related 11-gene signature for predicting prognosis and immune response in hepatocellular carcinoma.Medicine · 2026Article
- HER3 beyond the canonical paradigm: a versatile signaling hub in oncogenesis and therapeutic resistance.Journal of translational medicine · 2026Review
- CRISPR/Cas9 screenings reveal the role of STX1A and CDK1 in Cathepsin G entering and killing colorectal cancer cells.bioRxiv : the preprint server for biology · 2025Article
- HER3: Unmasking a twist in the tale of a previously unsuccessful therapeutic pursuit targeting a key cancer survival pathway.Genes & diseases · 2025Review
- Emerging importance of HER3 in tumorigenesis and cancer therapy.Nature reviews. Clinical oncology · 2025Review
- cAMP response element-binding protein: A credible cancer drug target.The Journal of pharmacology and experimental therapeutics · 2025Review
- Oncogenic activation ofGenes & diseases · 2025Review
- CRISPR/Cas9 Screenings Reveal the Role of STX1A and CDK1 in Cathepsin G Entering and Killing Colorectal Cancer Cells.Interdisciplinary information sciences · 2025Article
- RSK1 and RSK2 as therapeutic targets: an up-to-date snapshot of emerging data.Expert opinion on therapeutic targets · 2024Review
- Comprehensive profiling of extrachromosomal circular DNAs in colorectal cancer progression.Scientific reports · 2024Article
- NKX2‑1 copy number alterations are associated with oncogenic, immunological and prognostic remodeling in non‑small cell lung cancer.Oncology letters · 2024Article
- Neutrophil extracellular traps induced by chemotherapy inhibit tumor growth in murine models of colorectal cancer.The Journal of clinical investigation · 2024Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
How PD-L1 expression is regulated in cancer is poorly understood. Here, we report that the ATP-binding activity of ERBB3 pseudokinase regulates PD-L1 gene expression in colorectal cancers (CRCs). ERBB3 is one of the four members of the EGF receptor family, all with protein tyrosine kinase domains. ERBB3 is a pseudokinase with a high binding affinity to ATP. We showed that ERBB3 ATP-binding inactivation mutant reduces tumorigenicity in genetically engineered mouse models and impairs xenograft tumor growth of CRC cell lines. The ERBB3 ATP-binding mutant cells dramatically reduce IFN-γ-induced PD-L1 expression. Mechanistically, ERBB3 regulates IFN-γ-induced PD-L1 expression through the IRS1-PI3K-PDK1-RSK-CREB signaling axis. CREB is the transcription factor that regulates PD-L1 gene expression in CRC cells. Knockin of a tumor-derived ERBB3 mutation located in the kinase domain sensitizes mouse colon cancers to anti-PD1 antibody therapy, suggesting that ERBB3 mutations could be predictive biomarkers for tumors amenable to immune checkpoint therapy.
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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.