Increased Expression of Phosphorylated FADD in Anaplastic Large Cell and Other T-Cell Lymphomas

Patel, Suketu; Murphy, Derek; Haralambieva, Eugenia; Abdulla, Zainalabideen A.; Wong, Kah Keng; Chen, Hong; Gould, Edith; Roncador, Giovanna; Hatton, Chris; Anderson, Amanda P.; Banham, Alison H.; Pulford, Karen

doi:10.4137/bmi.s16553

Cited by 7 publications

(9 citation statements)

References 54 publications

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“…However, a considerable inter-tumor heterogeneity was observed. A similar scenario has been previously reported in T-cell tumors and B-cell non-Hodgkin lymphoma, where both phospho-FADD positivity and signal intensity exhibited a high variation [ 28 , 29 ].…”

Section: Discussionsupporting

confidence: 83%

“…These and other authors suggest that assessment of FADD phosphorylation may be useful as a prognostic biomarker, and that induction of FADD phosphorylation could be a target in cancer therapy [ 39 ]. However, very limited results regarding FADD phosphorylation are available in hematological human cancers [ 29 ]. We report here that murine T-LBL samples exhibit a pronounced reduction of S191-phospho-FADD, thus resulting the ratio [S191-P-FADD/FADD] considerably diminished.…”

Section: Discussionmentioning

confidence: 99%

“…FADD phosphorylation has been analyzed in numerous solid tumors, however very limited and heterogeneous results are available in hematological cancers [ 28 , 29 ]. Thus, whether alterations in FADD expression and phosphorylation are involved in T-cell lymphoblastic lymphoma kept an unresolved question.…”

Section: Introductionmentioning

confidence: 99%

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Deregulated FADD expression and phosphorylation in T-cell lymphoblastic lymphoma

et al. 2016

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In the present work, we show that T-cell lymphoblastic lymphoma cells exhibit a reduction of FADD availability in the cytoplasm, which may contribute to impaired apoptosis. In addition, we observe a reduction of FADD phosphorylation that inversely correlates with the proliferation capacity and tumor aggressiveness. The resultant balance between FADD-dependent apoptotic and non-apoptotic abilities may define the outcome of the tumor. Thus, we propose that FADD expression and phosphorylation can be reliable biomarkers with prognostic value for T-LBL stratification.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

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Deregulated FADD expression and phosphorylation in T-cell lymphoblastic lymphoma

et al. 2016

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“…For example, increased phosphorylation of FADD has been implicated in poor prognosis in lung adenocarcinoma [32]. Additional observations supporting the pro-survival role of phosphorylated FADD in cancer is the report that inhibition of FADD phosphorylation increases cisplatin-induced cell death in A549 lung cancer cells [33] and the report of increased FADD phosphorylation in T cell lymphomas [34]. Furthermore, FADD gene amplification and FADD overexpression has been reported in oral squamous cell carcinoma [35].…”

Section: Discussionmentioning

confidence: 94%

Knock down of Fas-Associated Protein with Death Domain (FADD) Sensitizes Osteosarcoma to TNFα-induced Cell Death

et al. 2020

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Fas-associated protein with death domain (FADD) was first identified for its role in linking death receptors to the apoptotic signaling pathway with subsequent cell death. Later studies reported non-apoptotic functions for FADD in normal cells and cancer cells. Non-apoptotic functions for FADD in osteosarcoma (OS) have not been reported. In this study, FADD protein expression was knocked down in human CCHOSD, LM7, and SaOS2 OS cell lines followed by assessment of sensitivity to TNFα-or TRAIL-induced cell death. Knock down of FADD significantly increased TNFα-induced cell death in LM7 and SaOS2 cell lines. The mode of TNFα-induced cell death was apoptosis and not necroptosis. Inhibition of nuclear factor kappa B (NFκB) in wildtype cells increased TNFα-induced cell death to similar levels observed in FADD knockdown cells, suggesting a role for FADD in NFκB pro-survival cell signaling. In addition, knock down of FADD increased SMAC mimetic-mediated TNFα-induced cell death in all cell lines studied. The results of this study indicate that FADD has a pro-survival function in OS following TNFα treatment that involves NFκB signaling. The results also indicate that the pro-survival function of FADD is associated with XIAP activity.

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“…Phosphorylation in this serine has been reported to play a very important role in regulating cell growth and proliferation [37,88,90,98,99]. Moreover, the deregulation of FADD phosphorylation at serine 194 has been identified as a relevant clinical issue in several types of hematological [13,100,101] and solid cancers [5,7,37,88,90,98,99,102,103]. A molecular mechanism associating the increase in phosphorylated FADD with tumorigenesis has been hinted at only in limited studies.…”

Section: Posttranslational Modifications Of Fadd Proteinmentioning

confidence: 99%

FADD in Cancer: Mechanisms of Altered Expression and Function, and Clinical Implications

Marín-Rubio

Vela‐Martín

Fernández‐Piqueras

et al. 2019

Cancers

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FADD was initially described as an adaptor molecule for death receptor-mediated apoptosis, but subsequently it has been implicated in nonapoptotic cellular processes such as proliferation and cell cycle control. During the last decade, FADD has been shown to play a pivotal role in most of the signalosome complexes, such as the necroptosome and the inflammasome. Interestingly, various mechanisms involved in regulating FADD functions have been identified, essentially posttranslational modifications and secretion. All these aspects have been thoroughly addressed in previous reviews. However, FADD implication in cancer is complex, due to pleiotropic effects. It has been reported either as anti- or protumorigenic, depending on the cell type. Regulation of FADD expression in cancer is a complex issue since both overexpression and downregulation have been reported, but the mechanisms underlying such alterations have not been fully unveiled. Posttranslational modifications also constitute a relevant mechanism controlling FADD levels and functions in tumor cells. In this review, we aim to provide detailed, updated information on alterations leading to changes in FADD expression and function in cancer. The participation of FADD in various biological processes is recapitulated, with a mention of interesting novel functions recently proposed for FADD, such as regulation of gene expression and control of metabolic pathways. Finally, we gather all the available evidence regarding the clinical implications of FADD alterations in cancer, especially as it has been proposed as a potential biomarker with prognostic value.

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Increased Expression of Phosphorylated FADD in Anaplastic Large Cell and Other T-Cell Lymphomas

Cited by 7 publications

References 54 publications

Deregulated FADD expression and phosphorylation in T-cell lymphoblastic lymphoma

Deregulated FADD expression and phosphorylation in T-cell lymphoblastic lymphoma

Knock down of Fas-Associated Protein with Death Domain (FADD) Sensitizes Osteosarcoma to TNFα-induced Cell Death

FADD in Cancer: Mechanisms of Altered Expression and Function, and Clinical Implications

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