ArticleThe Journal of biological chemistry2015
Epidermal growth factor receptor (EGFR) signaling requires a specific endoplasmic reticulum thioredoxin for the post-translational control of receptor presentation to the cell surface.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 72 citations in OpenAlex.
- Article
- Beyond Antioxidants: How Redox Pathways Shape Cellular Signaling and Disease Outcomes.Antioxidants (Basel, Switzerland) · 2025Review
- Non-Canonical, Strongly Selective Protein Disulfide Isomerases as Anticancer Therapeutic Targets.Biomolecules · 2025Review
- Proteogenomic characterisation of primary oral cancer unveils extracellular matrix remodelling and immunosuppressive microenvironment linked to lymph node metastasis.Clinical and translational medicine · 2025Article
- Bispecific antibody simultaneously targeting AGR2 and PD1 mediates cytotoxic T-cell-induced antitumor response in AGR2-dependent manner and inhibits AGR2-induced PDL1 upregulation.Scientific reports · 2025Article
- Disrupting AGR2/IGF1 paracrine and reciprocal signaling for pancreatic cancer therapy.Cell reports. Medicine · 2025Article
- AGR2-mediated unconventional secretion of 14-3-3ε and α-actinin-4, responsive to ER stress and autophagy, drives chemotaxis in canine mammary tumor cells.Cellular & molecular biology letters · 2024Article
- New insights into the unfolded protein response (UPR)-anterior gradient 2 (AGR2) pathway in the regulation of intestinal barrier function in weaned piglets.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2023Review
- AGR2: a secreted protein worthy of attention in diagnosis and treatment of breast cancer.Frontiers in oncology · 2023Review
- Protein Disulfide Isomerases Function as the Missing Link Between Diabetes and Cancer.Antioxidants & redox signaling · 2022Review
- Functions and mechanisms of protein disulfide isomerase family in cancer emergence.Cell & bioscience · 2022Review
- QKI-6 Suppresses Cell Proliferation, Migration, and EMT in Non-Small Cell Lung Cancer.Frontiers in oncology · 2022Article
- Serum Level of Tumor-Overexpressed AGR2 Is Significantly Associated with Unfavorable Prognosis of Canine Malignant Mammary Tumors.Animals : an open access journal from MDPI · 2021Article
- Effects of ER-resident and secreted AGR2 on cell proliferation, migration, invasion, and survival in PANC-1 pancreatic cancer cells.BMC cancer · 2021Article
- The Secreted Protein Disulfide Isomerase Ag1 Lost by Ancestors of Poorly Regenerating Vertebrates Is Required forFrontiers in cell and developmental biology · 2021Article
- Secretion of pro-oncogenic AGR2 protein in cancer.Heliyon · 2020Review
- Growth Factors in Regeneration and Regenerative Medicine: "the Cure and the Cause".Frontiers in endocrinology · 2020Review
- Zwitterionic near-infrared fluorophore-conjugated epidermal growth factor for fast, real-time, and target-cell-specific cancer imaging.Theranostics · 2019Article
- A critical role of the thioredoxin domain containing protein 5 (TXNDC5) in redox homeostasis and cancer development.Genes & diseases · 2018Review
- Sortilin as a new membrane inhibitor of EGFR trafficking for overcoming resistance to EGFR inhibitors in non-small cell lung cancer.Journal of thoracic disease · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The epidermal growth factor receptor (EGFR) is a well characterized receptor-tyrosine kinase that functions in development and serves a vital role in many human cancers. Understanding EGFR regulatory mechanisms, and hence approaches for clinical intervention, has focused on ligand-receptor interactions and tyrosine kinase activity. Here, we show using the NCI-H460 lung and A431 epidermoid human cancer cell lines that EGFR binding to anterior gradient homolog 2 (AGR2) in the endoplasmic reticulum is required for receptor delivery to the plasma membrane and thus EGFR signaling. Reduced AGR2 protein levels or mutation of an essential cysteine in the active site result in decreased cell surface EGFR and a concomitant decrease in signaling as reflected by AREG, EGR1, and FOS expression. Similar to previously described EGFR nulls, an AGR2 null also resulted in embryonic lethality. Consistent with its role in regulating EGFR-mediated signaling, AGR2 expression is also enhanced in many human cancers and promotes the transformed phenotype. Furthermore, EGFR-mediated signaling in NCI-H460 cells, which are resistant to the tyrosine kinase inhibitor AG1478, is also disrupted with reduced AGR2 expression. The results provide insights into why cancer prognosis or response to therapy often does not correlate with EGFR protein or RNA levels because they do not reflect delivery to the cell surface where signaling is initiated. AGR2, therefore, represents a novel post-translational regulator of EGFR-mediated signaling and a promising target for treating human cancers.
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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.