The pro-apoptotic Bcl-2 family member Harakiri (HRK) induces cell death in glioblastoma multiforme
| Autor: | Filiz Senbabaoglu, Ezgi Kaya-Aksoy, Fidan Seker, Tolga Lokumcu, Sercin Karahuseyinoglu, Gizem Nur Sahin, Tugba Bagci-Onder, Ilknur Sur-Erdem, Ahmet Cingoz, Alisan Kayabolen |
|---|---|
| Přispěvatelé: | Önder, Tuğba Bağcı (ORCID 0000-0003-3646-2613 & YÖK ID 184359), Kaya-Aksoy, Ezgi, Cingöz, Ahmet, Şenbabaoğlu, Filiz, Şeker, Fidan, Sur-Erdem, İlknur, Kayabölen, Alişan, Lokumcu, Tolga, Şahin, Gizem Nur, Karahseyinoglu, Sercin (ORCID 0000-0001-5531-2587 & YÖK ID 110772), School of Medicine, Department of Physiology, Department of Histology and Embryology |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Programmed cell death medicine.drug_class Immunology Biology lcsh:RC254-282 Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine medicine Gene silencing lcsh:QH573-671 lcsh:Cytology Promoter methylation Cancer Trail Glioma Interacts Proteins Survival Domain Dp5 Bcl-2 family Histone deacetylase inhibitor Cell Biology Medicine Cell biology lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Phenotype 030104 developmental biology Cell culture Apoptosis 030220 oncology & carcinogenesis Cancer research Tumor necrosis factor alpha |
| Zdroj: | Cell Death Discovery, Vol 5, Iss 1, Pp 1-12 (2019) Cell Death Discovery |
| ISSN: | 2058-7716 |
| DOI: | 10.1038/s41420-019-0144-z |
| Popis: | Harakiri (HRK) is a BH3-only protein of the Bcl-2 family and regulates apoptosis by interfering with anti-apoptotic Bcl-2 and Bcl-xL proteins. While its function is mainly characterized in the nervous system, its role in tumors is ill-defined with few studies demonstrating HRK silencing in tumors. In this study, we investigated the role of HRK in the most aggressive primary brain tumor, glioblastoma multiforme (GBM). We showed that HRK is differentially expressed among established GBM cell lines and that HRK overexpression can induce apoptosis in GBM cells at different levels. This phenotype can be blocked by forced expression of Bcl-2 and Bcl-xL, suggesting the functional interaction of Bcl-2/ Bcl-xL and HRK in tumor cells. Moreover, HRK overexpression cooperates with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a known tumor-specific pro-apoptotic agent. Besides, secondary agents that augment TRAIL response, such as the histone deacetylase inhibitor MS-275, significantly increases HRK expression. In addition, GBM cell response to TRAIL and MS-275 can be partly abolished by HRK silencing. Finally, we showed that HRK induction suppresses tumor growth in orthotopic GBM models in vivo, leading to increased survival. Taken together, our results suggest that HRK expression is associated with GBM cell apoptosis and increasing HRK activity in GBM tumors might offer new therapeutic approaches. Scientific and Technological Research Council of Turkey (TÜBİTAK); Marie Curie FP7 Career Reintegration Grant; European Union (European Union); H2020; Unesco L'oreal Women in Science Grant; BAGEP |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|