ArticleCancer medicine2018
EGFR confers radioresistance in human oropharyngeal carcinoma by activating endoplasmic reticulum stress signaling PERK-eIF2α-GRP94 and IRE1α-XBP1-GRP78.
Article in Cancer medicine, 2018. 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, 35 citations in OpenAlex.
- Regulatory Mechanisms of XBP1 in Tumorigenesis and Cancer Progression: Challenges and Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Functional pH-Responsive Nanoparticles for Immune Reprogramming in MSS Colorectal Cancer via ER Stress-Induced Proteostasis Disruption, PD-L1-Targeting miRNA, and TLR7 Activation.Pharmaceutics · 2025Article
- MiR-204-5p mediates PERK inhibition to suppress growth and induce apoptosis in ovarian cancer through the eIF2α/ATF-4/CHOP pathway.Scientific reports · 2025Article
- TLR4 mediates lipotoxic β-cell dysfunction by inhibiting the TMEM24/PI3K/AKT pathway.Acta biochimica et biophysica Sinica · 2025Article
- Article
- NCancer gene therapy · 2025Article
- A synthetic molecule targeting STAT3 against human oral squamous cell carcinoma cells.International journal of medical sciences · 2025Article
- Pharmacological Inhibition of Epidermal Growth Factor Receptor Prevents Intracranial Aneurysm Rupture by Reducing Endoplasmic Reticulum Stress.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Prognostic stratification of oropharyngeal cancer patients in a betel nut chewing and low HPV area.Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale · 2023Article
- Activating mutations in EGFR and PI3K promote ATF4 induction for NSCLC cell survival during amino acid deprivation.Heliyon · 2023Article
- Radiotherapy as a means to increase the efficacy of T-cell therapy in solid tumors.Oncoimmunology · 2023Review
- Extracts of Bauhinia Championii Alleviate Acute Neuronal Injury After Ischemic Reperfusion by Improving Endoplasmic Reticulum Stress-Mediated Neuronal Apoptosis.Current medical science · 2022Article
- Radiosensitizer EXO-miR-197-3p Inhibits Nasopharyngeal Carcinoma Progression and Radioresistance by Regulating the AKT/mTOR Axis and HSPA5-mediated Autophagy.International journal of biological sciences · 2022Article
- Biological Adaptations of Tumor Cells to Radiation Therapy.Frontiers in oncology · 2021Review
- Comprehensive analysis reveals GRP94 is associated with worse prognosis of breast cancer.Translational cancer research · 2021Article
- The Prognostic Value of PERK in Cancer and Its Relationship With Immune Cell Infiltration.Frontiers in molecular biosciences · 2021Article
- Endoplasmic reticulum stress serves an important role in cardiac ischemia/reperfusion injury (Review).Experimental and therapeutic medicine · 2020Review
- EGFR targeting enhances the efficiency of chemotherapy through inhibiting IRE1α-XBP1s pathway in colorectal cancer cells.Journal of Cancer · 2020Article
- Withaferin A triggers G2/M arrest and intrinsic apoptosis in glioblastoma cells via ATF4-ATF3-CHOP axis.Cell proliferation · 2020Article
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Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The activation of epidermal growth factor receptor (EGFR) is associated with radioresistance in malignant tumors. Specifically, radiation can destroy endoplasmic reticulum (ER) homeostasis to induce ER stress (ERS). However, the effect of EGFR-mediated regulation of ERS signaling pathway on radiosensitivity has not yet been reported. The present study showed that silencing EGFR increased radiosensitivity of both radiosensitive and radioresistant oropharyngeal squamous cell carcinoma (OSCC) cells by inhibiting ER stress signaling (PERK-eIF2α-GRP94 and IRE1α-XBP1-GRP78). This effect was abolished by pretreatment with EGF, however. In addition, knockdown of EGFR in OSCC cells inhibited DNA double-stand break repair and autophagy while increased radiation-induced apoptosis. Conversely, activating ERS inhibited the aforementioned functions. Furthermore, EGF increased ER stress-independent ERK and AKT signaling upon irradiation of OSCC cells. Immunohistochemical analysis of 80 tissue samples from OSCC patients showed that co-expression of EGFR and PERK was associated with poor prognosis. It thus appears EGFR confers radioresistance in OSCC by activating ER stress signaling. These results suggested that the cooperative effects of radiotherapy and EGFR-targeted inhibitor therapy can be further improved by inhibiting PERK-eIF2α-GRP94 and IRE1α-GRP78 in non-response oropharyngeal carcinoma patients.
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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.