The CD95/CD95L Signaling Pathway: A Role in Carcinogenesis

Fouqué, Amélie; Legembre, Patrick

doi:10.1007/978-3-662-44006-3_9

Cited by 7 publications

(10 citation statements)

References 173 publications

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“…The rationale for this treatment was found in experimental data that indicated that IVIgs are capable of preventing and treating bleomycin-induced pulmonary fibrosis in mice through the reduced expression of collagen-I protein in the affected lungs [23, 24]. Postulated mechanisms of this anti-fibrotic action of IVIg include modulation of cytokine production, inhibition of the complement reaction and inhibition of the CD95 receptor (Fas) activity through the presence of anti-Fas antibodies in IVIg [23, 54, 55]. Subsequently, one dose of cyclophosphamide, a nitrogen mustard alkylating and lymphocyte-modulating agent, was administered.…”

Section: Discussionmentioning

confidence: 99%

Prognosis and treatment of FOLFOX therapy related interstitial pneumonia: a plea for multimodal immune modulating therapy in the respiratory insufficient patient

et al. 2017

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Background: The FOLFOX regimen, i.e., folinic acid (FOL), fluorouracil (F) and oxaliplatin (OX), is a drug cocktail that is used to treat gastric and colorectal cancers. Despite the concomitant improvements in response rate, duration of response and patient survival, reports of serious toxic pulmonary side effects have progressively emerged. Case presentation: We describe a patient who was treated with FOLFOX as an adjuvant to a rectosigmoidal resection of a rectosigmoidal carcinoma and who developed respiratory insufficiency requiring mechanical ventilation. Computed tomography (CT) imaging and open lung biopsy findings were compatible with interstitial pneumonia (IP). She received multimodal combination treatment (acetylcysteine, corticosteroids, immune globulins and cyclophosphamide) and survived. We performed a systematic literature search and reviewed all 45 reported cases of FOLFOX-related lung toxicity and/or pulmonary fibrosis for their clinical characteristics and their outcomes related to therapy. Conclusions: We found that for the 45 cases with available data, the median age was 70 years, and the male-female ratio was 3.5: 1. In the patients exhibiting only mild respiratory symptoms, discontinuation of the culprit drug (oxaliplatin) resulted in a 100% regression of the symptoms. However the prognosis of the respiratory insufficient patient proved to be grim: death occurred in 76.9% of the cases despite conventional treatment with corticosteroids. We therefore urge oncologists and critical care specialists not to limit their interventions to the discontinuation of chemotherapy, artificial ventilation, corticosteroids and glutathione replenishment and to consider the gradual introduction of additional immune-modulating agents whenever life-threatening respiratory symptoms in oxaliplatin-treated patients do not subside; all the more so considering the fact that our analysis showed that every patient who survived intubation and mechanical ventilation experienced a full clinical recovery.

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Section: Discussionmentioning

confidence: 99%

Prognosis and treatment of FOLFOX therapy related interstitial pneumonia: a plea for multimodal immune modulating therapy in the respiratory insufficient patient

et al. 2017

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“…However, FasL can be a potent pro‐tumorigenic inflammatory factor, inflammatory cells, Being attracted by stimulating the release and expression of inflammatory cytokines and chemokines. There is also evidence that Fas induce proliferation, invasion and cell survival (Fouqué, Debure, & Legembre, ). Therefore, Fas can have two completely opposite effects in CRC, suppressor, or stimulator of tumor growth and metastasis.…”

Section: Death Receptor Signaling Pathwaymentioning

confidence: 99%

Targeting the death receptor signaling pathway as a potential therapeutic target in the treatment of colorectal cancer

Marjaneh

Hassanian

Ghobadi

et al. 2018

Journal Cellular Physiology

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Despite advances in the diagnosis and treatment of colorectal cancer (CRC), it remains a major cause of cancer related death globally. There are currently no chemotherapeutic agents that have been found to eradicate the disease without adverse effects. A defect in the death receptor signaling pathway is a feature of CRC. The ligand of these receptors belongs to the tumor necrosis factor family, and that are particularly expressed by cells of the immune system, and that induce apoptosis in a caspase dependent manner. The fact that malignant cells are particularly sensitive to these ligands, compared to normal cells, has led to work on the assessment of compounds that activate this pathway in the treatment of CRC. Phase I trials have shown that these death receptor agonists are safe. Phase II and III trials are currently investigating the efficacy of these therapeutic agents in the treatment of CRC. In this review, we describe the biochemical death receptor signaling pathway and its relationship to CRC. We also summarize the current clinical studies that are targeting this signaling pathway in CRC treatment.

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“…When it comes to DRs, Fas/CD95 (also called APO-1) is considered to be the prototypic and major member of the death-receptor family, a subgroup of the TNFRSF, which also includes the TRAIL receptors TRAIL-R1 (a.k.a., DR4) and TRAIL-R2 (a.k.a., DR5) and can transmit apoptotic signals through the presence of a cytoplasmic DD [46,47]. The interaction of Fas/CD95 with its cognate ligand (FasL/CD95L) results in the following: 1) receptor oligomerization and aggregation; 2) recruitment of the adaptor protein FADD, through homotypic interaction between the DDs of both Fas/CD95 and FADD; and 3) subsequent binding of procaspase-8 or -10 to FADD through their respective DEDs that eventually leads to caspase-8/10 activation [48].…”

Section: Fas/cd95-mediated Apoptosismentioning

confidence: 99%

“…1) have been reported [89,90], with most of the mutations distributed within the Fas/CD95 DD [47,89]. Fas/CD95 mutations have only been detected in a minor percentage of MM patients, all of them located at the DD of the DR, and therefore, it is not a widespread feature but might contribute to the pathogenesis and progression of myeloma in some patients [91,92].…”

Section: Fas/cd95 In the Regulation Of Apoptosis In Hematologic Cellsmentioning

confidence: 99%

“…Fas/CD95 is also able to trigger nonapoptotic responses through mechanisms that are not well understood [47,[257][258][259]. There is growing evidence that Fas/CD95, DR4, and DR5 can also signal cell survival through stimulation of nonapoptotic pathways involving NF-kB stimulation [260][261][262] as well as tyrosine protein kinase and MAPK signaling pathways [263][264][265][266].…”

Section: Rafts and Nonapoptotic Fas/ Cd95 Signalingmentioning

confidence: 99%

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Lipid raft-mediated Fas/CD95 apoptotic signaling in leukemic cells and normal leukocytes and therapeutic implications

Gajate

Mollinedo

2015

Journal of Leukocyte Biology

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Plasma membrane is now recognized to contain tightly packed cholesterol/sphingolipid-rich domains, known as lipid or membrane rafts, which are more ordered than the surrounding lipid bilayer. Lipid rafts are crucial for the compartmentalization of signaling processes in the membrane, mostly involved in cell survival and immune response. However, in the last 15 years, a large body of evidence has also identified raft platforms as scaffolds for the recruitment and clustering of death receptor Fas/CD95 and downstream signaling molecules, leading to the concept of death-promoting lipid rafts. This raft-Fas/CD95 coclustering was first described at the early 2000s as the underlying mechanism for the proapoptotic action of the alkylphospholipid analog edelfosine in leukemic cells, hence facilitating protein-protein interactions and conveying apoptotic signals independently of Fas/CD95 ligand. Edelfosine induces apoptosis in hematologic cancer cells and activated T-lymphocytes. Fas/CD95 raft coclustering is also promoted by Fas/CD95 ligand, agonistic Fas/CD95 antibodies, and additional antitumor drugs. Thus, death receptor recruitment in rafts is a physiologic process leading to cell demise that can be pharmacologically modulated. This redistribution and local accumulation of apoptotic molecules in membrane rafts, which are usually accompanied by displacement of survival signaling molecules, highlight how alterations in the apoptosis/survival signaling balance in specialized membrane regions modulate cell fate. Membrane rafts might also modulate apoptotic and nonapoptotic death receptor signaling. Here, we discuss the role of lipid rafts in Fas/CD95-mediated apoptotic cell signaling in hematologic cancer cells and normal leukocytes, with a special emphasis on their involvement as putative therapeutic targets in cancer and autoimmune diseases.

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The CD95/CD95L Signaling Pathway: A Role in Carcinogenesis

Cited by 7 publications

References 173 publications

Prognosis and treatment of FOLFOX therapy related interstitial pneumonia: a plea for multimodal immune modulating therapy in the respiratory insufficient patient

Prognosis and treatment of FOLFOX therapy related interstitial pneumonia: a plea for multimodal immune modulating therapy in the respiratory insufficient patient

Targeting the death receptor signaling pathway as a potential therapeutic target in the treatment of colorectal cancer

Lipid raft-mediated Fas/CD95 apoptotic signaling in leukemic cells and normal leukocytes and therapeutic implications

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