ArticleCancer science2017
Endoplasmic reticulum stress pathway PERK-eIF2α confers radioresistance in oropharyngeal carcinoma by activating NF-κB.
Article in Cancer science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 51 citations in OpenAlex.
- Regulation of Endoplasmic Reticulum Stress Suppresses Early Pro-Tumorigenic Events During N-Nitrosodiethylamine-Induced Hepatocarcinogenesis.Journal of biochemical and molecular toxicology · 2026Article
- Propofol attenuates angiogenesis by activating endoplasmic reticulum stress to suppress TFAP2C-driven VEGFA transcription.Apoptosis : an international journal on programmed cell death · 2026Article
- RETRACTED: Plant rhabdovirus glycoprotein activates unfolded protein response-mediated antiviral ER-phagy in insect vectors.PLoS pathogens · 2026Article
- Beta-Caryophyllene Augments Radiotherapy Efficacy in GBM by Modulating Cell Apoptosis and DNA Damage Repair via PPARγ and NF-κB Pathways.Phytotherapy research : PTR · 2025Article
- NCancer gene therapy · 2025Article
- Endoplasmic reticulum stress in non-small cell lung cancer.American journal of cancer research · 2025Review
- Interplay Between Key Molecular Signaling Pathways and Immune Players Following Brain Irradiation.Mediators of inflammation · 2025Review
- The roles and mechanisms of endoplasmic reticulum stress-mediated autophagy in animal viral infections.Veterinary research · 2024Review
- NCI 159456 PERK Inhibitor as a Targeted Therapy for Lung Cancer: An In Vitro Study.Biomedicines · 2024Article
- Flavopiridol Suppresses Cell Proliferation and Migration and Induces Apoptotic Cell Death by Inhibiting Oncogenic FOXM1 Signaling in IDH Wild-Type and IDH-Mutant GBM Cells.Molecular neurobiology · 2024Article
- Targeting endoplasmic reticulum stress signaling in ovarian cancer therapy.Cancer biology & medicine · 2023Review
- Endoplasmic reticulum stress contributes to cisplatin-induced chronic kidney disease via the PERK-PKCδ pathway.Cellular and molecular life sciences : CMLS · 2022Article
- The Role of Endoplasmic Reticulum Stress and NLRP3 Inflammasome in Liver Disorders.International journal of molecular sciences · 2022Review
- PERK Regulates the Sensitivity of Hepatocellular Carcinoma Cells to High-LET Carbon Ions via either Apoptosis or Ferroptosis.Journal of Cancer · 2022Article
- A combination of sorafenib and radiotherapy reduces NF-κB activity and growth of hepatocellular carcinoma in an orthotopic mouse model.Oncology letters · 2021Article
- Biological Adaptations of Tumor Cells to Radiation Therapy.Frontiers in oncology · 2021Review
- Clinical and Preclinical Outcomes of Combining Targeted Therapy With Radiotherapy.Frontiers in oncology · 2021Review
- Role of RONS and eIFs in Cancer Progression.Oxidative medicine and cellular longevity · 2021Review
- Interplay between endoplasmic reticulum stress and non-coding RNAs in cancer.Journal of hematology & oncology · 2020Review
- PERK controls bone homeostasis through the regulation of osteoclast differentiation and function.Cell death & disease · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum stress (ERS) plays an important role in the pathogenesis and development of malignant tumors, as well as in the regulation of radiochemoresistance and chemoresistance in many malignancies. ERS signaling pathway protein kinase RNA-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor-2 (eIF2α) may induce aberrant activation of nuclear factor-κB (NF-κB). Our previous study showed that NF-κB conferred radioresistance in lymphoma cells. However, whether PERK-eIF2α regulates radioresistance in oropharyngeal carcinoma through NF-κB activation is unknown. Herein, we showed that PERK overexpression correlated with a poor prognosis for patients with oropharyngeal carcinoma (P < 0.01). Meanwhile, the percentage of the high expression level of PERK in oropharyngeal carcinoma patients resistant to radiation was higher than in patients sensitive to radiation (77.7 and 33.3%, respectively; P < 0.05). Silencing PERK and eIF2α increased the radiosensitivity in oropharyngeal carcinoma cells and increased radiation-induced apoptosis and G2/M phase arrest. PERK-eIF2α silencing also inhibited radiation-induced NF-κB phosphorylation and increased the DNA double strand break-related proteins ATM phosphorylation. NF-κB activator TNF-α and the ATM inhibitor Ku55933 offset the regulatory effect of eIF2α on the expression of radiation-induced cell apoptosis-related proteins and the G2/M phase arrest-related proteins. These data indicate that PERK regulates radioresistance in oropharyngeal carcinoma through NF-kB activation-mediated phosphorylation of eIF2α, enhancing X-ray-induced activation of DNA DSB repair, cell apoptosis inhibition and G2/M cell cycle arrest.
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