Dual role of ER stress in response to metabolic co-targeting and radiosensitivity in head and neck cancer cells
| العنوان: | Dual role of ER stress in response to metabolic co-targeting and radiosensitivity in head and neck cancer cells |
|---|---|
| المؤلفون: | F. Manig, Michael Baumann, Oleg Chen, Oleh V. Stasyk, Zhanru Yu, Leoni A. Kunz-Schughart, Benedikt M. Kessler, Anna Dubrovska, Loreen Lehmann, Nagwa Sorour, Steffen Löck |
| المصدر: | Cellular and Molecular Life Sciences 78(2021), 3021-3044 Cellular and Molecular Life Sciences |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Arginine, Eukaryotic Initiation Factor-2, Cell Culture Techniques, Apoptosis, Radiation Tolerance, Arginine-deprivation therapy, chemistry.chemical_compound, 0302 clinical medicine, RNA, Small Interfering, Chemistry, Endoplasmic Reticulum Stress, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Molecular Medicine, Original Article, RNA Interference, ER stress, Canavanine, Signal Transduction, Head and neck squamous carcinoma, Metabolic targeting, Protein Serine-Threonine Kinases, 03 medical and health sciences, Cellular and Molecular Neuroscience, Cell Line, Tumor, 3-D culture, Endoribonucleases, medicine, Humans, Radiosensitivity, Molecular Biology, Cell Proliferation, Radiosensitization, Pharmacology, Squamous Cell Carcinoma of Head and Neck, X-Rays, Head and neck cancer, Cell Biology, medicine.disease, Activating Transcription Factor 4, Head and neck squamous-cell carcinoma, Culture Media, 030104 developmental biology, Cancer cell, Unfolded protein response, Cancer research, Transcription Factor CHOP |
| الوصف: | Arginine deprivation therapy (ADT) is a new metabolic targeting approach with high therapeutic potential for various solid cancers. Combination of ADT with low doses of the natural arginine analog canavanine effectively sensitizes malignant cells to irradiation. However, the molecular mechanisms determining the sensitivity of intrinsically non-auxotrophic cancers to arginine deficiency are still poorly understood. We here show for the first time that arginine deficiency is accompanied by global metabolic changes and protein/membrane breakdown, and results in the induction of specific, more or less pronounced (severe vs. mild) ER stress responses in head and neck squamous cell carcinoma (HNSCC) cells that differ in their intrinsic ADT sensitivity. Combination of ADT with canavanine triggered catastrophic ER stress via the eIF2α-ATF4(GADD34)-CHOP pathway, thereby inducing apoptosis; the same signaling arm was irrelevant in ADT-related radiosensitization. The particular strong supra-additive effect of ADT, canavanine and irradiation in both intrinsically more and less sensitive cancer cells supports the rational of ER stress pathways as novel target for improving multi-modal metabolic anti-cancer therapy. Electronic supplementary material The online version of this article (10.1007/s00018-020-03704-7) contains supplementary material, which is available to authorized users. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::df213edef1933636ae00b4bbabbdef14Test https://www.hzdr.de/publications/Publ-33956-1Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....df213edef1933636ae00b4bbabbdef14 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |