ArticleThe Journal of experimental medicine2004
c-FLIP mediates resistance of Hodgkin/Reed-Sternberg cells to death receptor-induced apoptosis.
Article in The Journal of experimental medicine, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 198 citations in OpenAlex.
- Disordered differentiation and cellular senescence in pediatric Hodgkin Reed-Sternberg cells.Blood advances · 2026Article
- c-FLIP as a master regulator of immune homeostasis and disease mechanisms.Cell death & disease · 2026Review
- Anoikis: To Die or Not to Die?International journal of molecular sciences · 2026Review
- Protective efficacy of emodin in Swiss Albino mice induced with Dalton Ascitic lymphoma.3 Biotech · 2025Article
- Article
- EX527, a sirtuins 1 inhibitor, sensitizes T-cell leukemia to death receptor-mediated apoptosis by downregulating cellular FLICE inhibitory protein.Cancer biology & therapy · 2024Article
- The Identification of New c-FLIP Inhibitors for Restoring Apoptosis in TRAIL-Resistant Cancer Cells.Current issues in molecular biology · 2024Article
- Hodgkin Lymphoma: A Special Microenvironment.Journal of clinical medicine · 2021Review
- Essential role of the linear ubiquitin chain assembly complex and TAK1 kinase in A20 mutant Hodgkin lymphoma.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Efficient recruitment of c-FLIPCancer science · 2020Article
- Immune and Inflammatory Cells of the Tumor Microenvironment Represent Novel Therapeutic Targets in Classical Hodgkin Lymphoma.International journal of molecular sciences · 2019Review
- c-FLIP and CD95 signaling are essential for survival of renal cell carcinoma.Cell death & disease · 2019Article
- Formation of the Immunosuppressive Microenvironment of Classic Hodgkin Lymphoma and Therapeutic Approaches to Counter It.International journal of molecular sciences · 2019Review
- Caspase-8: A Novel Target to Overcome Resistance to Chemotherapy in Glioblastoma.International journal of molecular sciences · 2018Review
- Acquired Natural Killer Cell Dysfunction in the Tumor Microenvironment of Classic Hodgkin Lymphoma.Frontiers in immunology · 2018Review
- Increased cFLIP expression in thymic epithelial tumors blocks autophagy via NF-κB signalling.Oncotarget · 2017Article
- Invariant Natural Killer T Cells in Immune Regulation of Blood Cancers: Harnessing Their Potential in Immunotherapies.Frontiers in immunology · 2017Review
- A roadmap of constitutive NF-κB activity in Hodgkin lymphoma: Dominant roles of p50 and p52 revealed by genome-wide analyses.Genome medicine · 2016Article
- RIP1 Cleavage in the Kinase Domain Regulates TRAIL-Induced NF-κB Activation and Lymphoma Survival.Molecular and cellular biology · 2015Article
- Lymphoma: immune evasion strategies.Cancers · 2015Review
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to death receptor-mediated apoptosis is supposed to be important for the deregulated growth of B cell lymphoma. Hodgkin/Reed-Sternberg (HRS) cells, the malignant cells of classical Hodgkin's lymphoma (cHL), resist CD95-induced apoptosis. Therefore, we analyzed death receptor signaling, in particular the CD95 pathway, in these cells. High level CD95 expression allowed a rapid formation of the death-inducing signaling complex (DISC) containing Fas-associated death domain-containing protein (FADD), caspase-8, caspase-10, and most importantly, cellular FADD-like interleukin 1beta-converting enzyme-inhibitory protein (c-FLIP). The immunohistochemical analysis of the DISC members revealed a strong expression of CD95 and c-FLIP overexpression in 55 out of 59 cases of cHL. FADD overexpression was detectable in several cases. Triggering of the CD95 pathway in HRS cells is indicated by the presence of CD95L in cells surrounding them as well as confocal microscopy showing c-FLIP predominantly localized at the cell membrane. Elevated c-FLIP expression in HRS cells depends on nuclear factor (NF)-kappaB. Despite expression of other NF-kappaB-dependent antiapoptotic proteins, the selective down-regulation of c-FLIP by small interfering RNA oligoribonucleotides was sufficient to sensitize HRS cells to CD95 and tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. Therefore, c-FLIP is a key regulator of death receptor resistance in HRS cells.
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