ArticleMolecular and cellular endocrinology2016
Anticipatory activation of the unfolded protein response by epidermal growth factor is required for immediate early gene expression and cell proliferation.
Article in Molecular and cellular endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Predicting diagnostic gene biomarkers in allergic asthma.Medicine · 2026Article
- The role of UPR-related long noncoding RNAs in development of endocrine resistance in breast cancer.International journal of cancer · 2025Review
- EGF/ERBB2 blocks the endoplasmic reticulum-associated degradation to facilitate chronic obstructive pulmonary disease development by decreasing FAM8A1 via up-regulating DNMT3A.Functional & integrative genomics · 2025Article
- Single-cell transcriptomics identifies PDIA4 as a marker of progression and therapeutic vulnerability in multiple myeloma.Journal of translational medicine · 2025Article
- Targeting the SYVN1-EGFR axis: a breakthrough strategy for TKI-resistant NSCLC.Cell death & disease · 2025Article
- Prognostic Value of GPNMB, EGFR, p-PI3K, and Ki-67 in Patients with Esophageal Squamous Cell Carcinoma.Analytical cellular pathology (Amsterdam) · 2022Article
- New insights into the interplay between autophagy and oxidative and endoplasmic reticulum stress in neuronal cell death and survival.Frontiers in cell and developmental biology · 2022Review
- Src couples estrogen receptor to the anticipatory unfolded protein response and regulates cancer cell fate under stress.Biochimica et biophysica acta. Molecular cell research · 2020Article
- Article
- Spatial and temporal alterations in protein structure by EGF regulate cryptic cysteine oxidation.Science signaling · 2020Article
- EGFR targeting enhances the efficiency of chemotherapy through inhibiting IRE1α-XBP1s pathway in colorectal cancer cells.Journal of Cancer · 2020Article
- Estrogen-independent Myc overexpression confers endocrine therapy resistance on breast cancer cells expressing ERαY537S and ERαD538G mutations.Cancer letters · 2019Article
- ER Stress and the UPR in Shaping Intestinal Tissue Homeostasis and Immunity.Frontiers in immunology · 2019Review
- EGFR confers radioresistance in human oropharyngeal carcinoma by activating endoplasmic reticulum stress signaling PERK-eIF2α-GRP94 and IRE1α-XBP1-GRP78.Cancer medicine · 2018Article
- Strong and sustained activation of the anticipatory unfolded protein response induces necrotic cell death.Cell death and differentiation · 2018Article
- Ethyl Acetate Extract ofInternational journal of molecular sciences · 2018Article
- Article
- A New Role for Estrogen Receptor α in Cell Proliferation and Cancer: Activating the Anticipatory Unfolded Protein Response.Frontiers in endocrinology · 2018Review
- Targeting protein quality control pathways in breast cancer.BMC biology · 2017Review
- Inhibition of GRP78 abrogates radioresistance in oropharyngeal carcinoma cells after EGFR inhibition by cetuximab.PloS one · 2017Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The onco-protein epidermal growth factor (EGF) initiates a cascade that includes activation of the ERK and AKT signaling pathways and alters gene expression. We describe a new action of EGF-EGF receptor (EGFR), rapid anticipatory activation of the endoplasmic reticulum stress sensor, the unfolded protein response (UPR). Within 2 min, EGF elicits EGFR dependent activation of phospholipase C γ (PLCγ), producing inositol triphosphate (IP3), which binds to IP3 receptor (IP3R), opening the endoplasmic reticulum IP3R Ca(2+) channels, resulting in increased intracellular Ca(2+). This calcium release leads to transient and moderate activation of the IRE1α and ATF6α arms of the UPR, resulting in induction of BiP chaperone. Knockdown or inhibition of EGFR, PLCγ or IP3R blocks the increase in intracellular Ca(2+). While blocking the increase in intracellular Ca(2+) by locking the IP3R calcium channel with 2-APB had no effect on EGF activation of the ERK or AKT signaling pathways, it abolished the rapid EGF-mediated induction and repression of gene expression. Knockdown of ATF6α or XBP1, which regulate UPR-induced chaperone production, inhibited EGF stimulated cell proliferation. Supporting biological relevance, increased levels of EGF receptor during tumor progression were correlated with increased expression of the UPR gene signature. Anticipatory activation of the UPR is a new role for EGF. Since UPR activation occurs in <2 min, it is an initial cell response when EGF binds EGFR.
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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.