ArticleBiochemical pharmacology2008
c-FLIP knockdown induces ligand-independent DR5-, FADD-, caspase-8-, and caspase-9-dependent apoptosis in breast cancer cells.
Article in Biochemical pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 81 citations in OpenAlex.
- Biological Functions and Clinical Implications of CFLAR: From Cell Death Mechanisms to Therapeutic Targeting in Immune Regulation.Journal of inflammation research · 2025Review
- HuR inhibition overcomes cFLIP-mediated doxorubicin resistance in triple-negative breast cancer.NPJ precision oncology · 2024Article
- RNA-binding protein HuR inhibition induces multiple programmed cell death in breast and prostate cancer.Cell communication and signaling : CCS · 2024Article
- Review
- Article
- Interaction between the Hepatitis B Virus and Cellular FLIP Variants in Viral Replication and the Innate Immune System.Viruses · 2022Review
- Review
- Induction of apoptosis on ovarian adenocarcinoma cells, A2780 by tricyclohexylphosphanegold (I) mercaptobenzoate derivatives via intrinsic and extrinsic pathways.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2021Article
- Embelin downregulated cFLIP in breast cancer cell lines facilitate anti-tumor effect of IL-1β-stimulated human umbilical cord mesenchymal stem cells.Scientific reports · 2021Article
- LUBAC Suppresses IL-21-Induced Apoptosis in CD40-Activated Murine B Cells and Promotes Germinal Center B Cell Survival and the T-Dependent Antibody Response.Frontiers in immunology · 2021Article
- FLIP(L): the pseudo-caspase.The FEBS journal · 2020Review
- Purified Tea (International journal of molecular sciences · 2020Article
- Next-generation hypomethylating agent SGI-110 primes acute myeloid leukemia cells to IAP antagonist by activating extrinsic and intrinsic apoptosis pathways.Cell death and differentiation · 2020Article
- Cell-mediated immune resistance in cancer.Cancer drug resistance (Alhambra, Calif.) · 2020Article
- Article
- Notch and breast cancer metastasis: Current knowledge, new sights and targeted therapy.Oncology letters · 2019Review
- ITCH-dependent proteasomal degradation of c-FLIP induced by the anti-HER3 antibody 9F7-F11 promotes DR5/caspase 8-mediated apoptosis of tumor cells.Cell communication and signaling : CCS · 2019Article
- c-FLIP and CD95 signaling are essential for survival of renal cell carcinoma.Cell death & disease · 2019Article
- Inhibitory Effects of Total Triterpenoid Saponins Isolated from the Seeds of the Tea Plant (Camellia sinensis) on Human Ovarian Cancer Cells.Molecules (Basel, Switzerland) · 2017Article
- Beet root juice protects against doxorubicin toxicity in cardiomyocytes while enhancing apoptosis in breast cancer cells.Molecular and cellular biochemistry · 2016Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
Cellular-FLICE inhibitory protein (c-FLIP) is an inhibitor of apoptosis downstream of the death receptors Fas, DR4, and DR5, and is expressed as long (c-FLIP(L)) and short (c-FLIP(S)) splice forms. We found that the knockdown of c-FLIP using small interfering RNA (siRNA) triggered ligand-independent caspase-8- and -9-dependent spontaneous apoptosis and decreased the proliferation of MCF-7 breast cancer cells. Further analysis revealed that an apoptotic inhibitory complex (AIC) comprised of DR5, FADD, caspase-8, and c-FLIP(L) exists in MCF-7 cells, and the absence of c-FLIP(L) from this complex induces DR5- and FADD-mediated caspase-8 activation in the death inducing signaling complex (DISC). c-FLIP(S) was not detected in the AIC, and using splice form-specific siRNAs we showed that c-FLIP(L) but not c-FLIP(S) is required to prevent spontaneous death signaling in MCF-7 cells. These results clearly show that c-FLIP(L) prevents ligand-independent death signaling and provides direct support for studying c-FLIP as a relevant therapeutic target for breast cancers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.