ArticleCell death discovery2019
The pro-apoptotic Bcl-2 family member Harakiri (HRK) induces cell death in glioblastoma multiforme.
Article in Cell death discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Loss of TRPV1 may shift capsaicin response from MAPK-CASC11-MYC protection to mitochondrial apoptosis in glioblastoma U87 cells.International journal of biological macromolecules · 2026Article
- Comparative analysis of metabolome and transcriptomes to explore the inhibited influence of sonodynamic therapy combined with lonidamine on hepatocellular carcinoma.Drug delivery · 2025Article
- Biomedical informatics analysis has revealed a novel hub gene of the HBx in the pathogenesis and progression of DLBCL.iScience · 2025Article
- Molecular mechanisms underlying HRK interaction with BCL-XL and BCL-2 reveal specificity determinants for BH3 mimetics.iScience · 2025Article
- Transcriptomic profiling of autophagy and apoptosis pathways in liver cancer cells treated with a new tyrosine kinase inhibitor PD161570.Molecular medicine reports · 2025Article
- Extended culture of 2D gastruloids to model human mesoderm development.Nature methods · 2025Article
- Estrogen influences class-switched memory B cell frequency only in humans with two X chromosomes.The Journal of experimental medicine · 2025Article
- Novel strategy for activating gene expression through triplex DNA formation targeting epigenetically suppressed genes.RSC chemical biology · 2024Article
- TFEB activation hallmarks antigenic experience of B lymphocytes and directs germinal center fate decisions.Nature communications · 2024Article
- Glioma Stem Cells Are Sensitized to BCL-2 Family Inhibition by Compromising Histone Deacetylases.International journal of molecular sciences · 2023Article
- Potential Mechanisms of Metformin-Induced Apoptosis in HeLa Cells.Biomolecules · 2023Article
- Ruthenium Complex HB324 Induces Apoptosis via Mitochondrial Pathway with an Upregulation of Harakiri and Overcomes Cisplatin Resistance in Neuroblastoma Cells In Vitro.International journal of molecular sciences · 2023Article
- CRISPR activation screen identifies TGFβ-associated PEG10 as a crucial tumor suppressor in Ewing sarcoma.Scientific reports · 2022Article
- HRK inhibits colorectal cancer cells proliferation by suppressing the PI3K/AKT/mTOR pathway.Frontiers in oncology · 2022Article
- Cabazitaxel suppresses the proliferation and promotes the apoptosis and radiosensitivity of castration-resistant prostate cancer cells by inhibiting PI3K/AKT pathway.American journal of translational research · 2022Article
- KP772 overcomes multiple drug resistance in malignant lymphoma and leukemia cells in vitro by inducing Bcl-2-independent apoptosis and upregulation of Harakiri.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2021Article
- A novel endoplasmic stress mediator, Kelch domain containing 7B (KLHDC7B), increased Harakiri (HRK) in the SubAB-induced apoptosis signaling pathway.Cell death discovery · 2021Article
- Opuntiol Inhibits Growth and Induces Apoptosis in Human Glioblastoma Cells by Upregulating Active Caspase 3 Expression.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Generation of TRAIL-resistant cell line models reveals distinct adaptive mechanisms for acquired resistance and re-sensitization.Oncogene · 2021Article
- In vitro contact guidance of glioblastoma cells on metallic biomaterials.Journal of materials science. Materials in medicine · 2021Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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