ArticleOncogene2008
Suppression of cFLIP is sufficient to sensitize human melanoma cells to TRAIL- and CD95L-mediated apoptosis.
Article in Oncogene, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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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
49 citing papers in PubMed, 99 citations in OpenAlex.
- The anti-tumour activity of TNF in melanoma is determined by cFLIP.Cell death & disease · 2026Article
- Review
- cFLIPCellular & molecular immunology · 2023Article
- Nano-TRAIL: a promising path to cancer therapy.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- The deubiquitinase Usp27x as a novel regulator of cFLIPApoptosis : an international journal on programmed cell death · 2022Article
- Kaempferol sensitizes tumor necrosis factor-related apoptosis-inducing ligand-resistance chronic myelogenous leukemia cells to apoptosis.Molecular biology reports · 2022Article
- Enhancing the Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Signaling and Arginine Deprivation in Melanoma.International journal of molecular sciences · 2021Review
- Small-Molecule Natural Product Physachenolide C Potentiates Immunotherapy Efficacy by Targeting BET Proteins.Cancer research · 2021Article
- Article
- Low expression of pro-apoptotic proteins Bax, Bak and Smac indicates prolonged progression-free survival in chemotherapy-treated metastatic melanoma.Cell death & disease · 2020Article
- miR-125b suppresses cellular proliferation by targeting c-FLIP in gallbladder carcinoma.Oncology letters · 2019Article
- c-FLIP and CD95 signaling are essential for survival of renal cell carcinoma.Cell death & disease · 2019Article
- Countering TRAIL Resistance in Melanoma.Cancers · 2019Review
- TRAILblazing Strategies for Cancer Treatment.Cancers · 2019Review
- TNF-alpha and metalloproteases as key players in melanoma cells aggressiveness.Journal of experimental & clinical cancer research : CR · 2018Article
- Maritoclax Enhances TRAIL-Induced Apoptosis via CHOP-Mediated Upregulation of DR5 and miR-708-Mediated Downregulation of cFLIP.Molecules (Basel, Switzerland) · 2018Article
- Sensitization of recombinant human tumor necrosis factor-related apoptosis-inducing ligand-resistant malignant melanomas by quercetin.Melanoma research · 2018Article
- N-glycosylation of mouse TRAIL-R restrains TRAIL-induced apoptosis.Cell death & disease · 2018Article
- Icariside II overcomes TRAIL resistance of melanoma cells through ROS-mediated downregulation of STAT3/cFLIP signaling.Oncotarget · 2016Article
- Onto better TRAILs for cancer treatment.Cell death and differentiation · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Death ligands such as tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and certain forms of CD95L are attractive therapeutic options for metastatic melanoma. Since knowledge about the regulation of death receptor sensitivity in melanoma is sparse, we have analysed these signaling pathways in detail. The loss of CD95 or TRAIL-R1, but not of TRAIL-R2, surface expression correlated with apoptosis sensitivity in a panel of melanoma cell lines. In contrast, the expression of proteins of the apical apoptosis signaling cascade (FADD, initiator caspases-8 and cFLIP) did not predict apoptosis sensitivity. Since both TRAIL-R1 and -R2 transmit apoptotic signals, we asked whether cFLIP, highly expressed in several of the cell lines tested, is sufficient to maintain resistance to TRAIL-R2-mediated apoptosis. Downregulation of cFLIP in TRAIL-R2-positive, TRAIL-resistant IGR cells dramatically increased TRAIL sensitivity. Conversely ectopic expression of cFLIP in TRAIL-sensitive, TRAIL-R2-expressing RPM-EP melanoma cells inhibited TRAIL- and CD95L-mediated cell death. Thus, modulation of cFLIP is sufficient to sensitize TRAIL-R2-expressing cells for TRAIL. Taken together, albeit expressing all proteins necessary for death receptor-mediated apoptosis, TRAIL-R1 negative melanoma cells cannot undergo TRAIL- or CD95L-induced apoptosis due to expression of cFLIP. Hence, cFLIP represents an attractive therapeutic target for melanoma treatment, especially in combination with TRAIL receptor agonists.
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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.