High expression of anti-apoptotic genes in grade I and II meningiomas

Tirapelli, Daniela Pretti da Cunha; Menezes, Sarah Bomfim; Franco, Indira Maynart; Lustosa, Isis Lacrose; Rodrigues, Alisson Mendes; Novais, Paulo Cézar; Santiago, Antônio César Mendes; Peria, Fernanda Maris; Serafini, Luciano Neder; Marinho, Alexandre; Carlotti, Carlos Gilberto; Colli, Benedicto Oscar; Tirapelli, Luís Fernando

doi:10.1590/0004-282x20170027

Cited by 4 publications

(3 citation statements)

References 29 publications

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“…FLIP has been shown to be overexpressed in a number of cancer types, including non‐small‐cell lung cancer (NSCLC) , colorectal cancer , pancreatic cancer , nasopharyngeal carcinoma , stomach cancer , meningiomas , urothelial cancer , prostate cancer , acute myeloid leukaemia , Burkitt's lymphoma , cervical carcinomas , ovarian carcinoma and breast cancer . It is also well established that the viral FLIP K13 has antiapoptotic activity and plays an important role in the pathogenesis of gamma‐herpesvirus HHV‐8‐associated tumours, including Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease .…”

Section: Flip Regulationmentioning

confidence: 99%

FLIP as a therapeutic target in cancer

2018

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One of the classic hallmarks of cancer is disruption of cell death signalling. Inhibition of cell death promotes tumour growth and metastasis, causes resistance to chemo‐ and radiotherapies as well as targeted agents, and is frequently due to overexpression of antiapoptotic proteins rather than loss of pro‐apoptotic effectors. FLIP is a major apoptosis‐regulatory protein frequently overexpressed in solid and haematological cancers, in which its high expression is often correlated with poor prognosis. FLIP, which is expressed as long (FLIP(L)) and short (FLIP(S)) splice forms, achieves its cell death regulatory functions by binding to FADD, a critical adaptor protein which links FLIP to the apical caspase in the extrinsic apoptotic pathway, caspase‐8, in a number of cell death regulating complexes, such as the death‐inducing signalling complexes (DISCs) formed by death receptors. FLIP also plays a key role (together with caspase‐8) in regulating another form of cell death termed programmed necrosis or ‘necroptosis’, as well as in other key cellular processes that impact cell survival, including autophagy. In addition, FLIP impacts activation of the intrinsic mitochondrial‐mediated apoptotic pathway by regulating caspase‐8‐mediated activation of the pro‐apoptotic Bcl‐2 family member Bid. It has been demonstrated that FLIP can not only inhibit death receptor‐mediated apoptosis, but also cell death induced by a range of clinically relevant chemotherapeutic and targeted agents as well as ionizing radiation. More recently, key roles for FLIP in promoting the survival of immunosuppressive tumour‐promoting immune cells have been discovered. Thus, FLIP is of significant interest as an anticancer therapeutic target. In this article, we review FLIP's biology and potential ways of targeting this important tumour and immune cell death regulator.

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Section: Flip Regulationmentioning

confidence: 99%

FLIP as a therapeutic target in cancer

2018

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“…Valnet-Rabier et al [77] showed that in 32 Burkitt's lymphoma cases, a mainly cytoplasmic pool of c-FLIP was highly correlated with poor patient outcome [77]. Several studies have identified c-FLIP as an independent adverse indicator in cancer and found both c-FLIP L and c-FLIP S play important roles in cancer patient treatment outcomes and that the expression of particular c-FLIP isoforms has prognostic clinical value [66,[78][79][80][81][82][83][84][85][86]. Ullenhag et al [87] showed in colorectal (CLR) cancer patients that c-FLIP L is an independent marker of poor prognosis.…”

Section: C-flip As a Valuable Prognostic Biomarker In Various Cancersmentioning

confidence: 99%

c-FLIP, a Novel Biomarker for Cancer Prognosis, Immunosuppression, Alzheimer's Disease, Chronic Obstructive Pulmonary Disease (COPD), and a Rationale Therapeutic Target

Safa¹,

Kamocki²,

Saadatzadeh³

et al. 2019

Biomark J

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Dysregulation of c-FLIP (cellular FADD-like IL-1β-converting enzyme inhibitory protein) has been shown in several diseases including cancer, Alzheimer's disease, and chronic obstructive pulmonary disease (COPD). c-FLIP is a critical anti-cell death protein often overexpressed in tumors and hematological malignancies and its increased expression is often associated with a poor prognosis. c-FLIP frequently exists as long (c-FLIP L ) and short (c-FLIP S ) isoforms, regulates its anti-cell death functions through binding to FADD (FAS associated death domain protein), an adaptor protein known to activate caspases-8 and -10 and links c-FLIP to several cell death regulating complexes including the death-inducing signaling complex (DISC) formed by various death receptors. c-FLIP also plays a critical role in necroptosis and autophagy. Furthermore, c-FLIP is able to activate several pathways involved in cytoprotection, proliferation, and survival of cancer cells through various critical signaling proteins. Additionally, c-FLIP can inhibit cell death induced by several chemotherapeutics, anti-cancer small molecule inhibitors, and ionizing radiation. Moreover, c-FLIP plays major roles in aiding the survival of immunosuppressive tumor-promoting immune cells and functions in inflammation, Alzheimer's disease (AD), and chronic obstructive pulmonary disease (COPD). Therefore, c-FLIP can serve as a versatile biomarker for cancer prognosis, a diagnostic marker for several diseases, and an effective therapeutic target. In this article, we review the functions of c-FLIP as an anti-apoptotic protein and negative prognostic factor in human cancers, and its roles in resistance to anticancer drugs, necroptosis and autophagy, immunosuppression, Alzheimer's disease, and COPD.

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“…Additionally, another protein and gene expression analysis focused on apoptotic pathways including c-FLIP, XIAP, Bcl-2, caspase 3, 8 and 9, cytochrome c, APAF 1 and Smac/DIABLO molecules reported low protein levels regarding caspases. The study group also identified a potential blocking of these apoptotic inducers mediated by c-FLIP inhibition on them [ 16 ]. Interestingly, specific polymorphisms affecting genes such as caspase 8, NF2, XRCC1, and BRIP1 are related to increased risk for meningioma rise [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Caspase 8 Expression Patterns in Meningiomas: A Tissue Microarray Digital Image Analysis

Roukas¹,

Kouzoupis²,

Spyropoulou³

et al. 2022

Cureus

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Background: Caspases (cysteine-aspartic proteases) represent a family of enzymes that critically influence cell homeostasis by being involved in inflammation and apoptosis mechanisms. Meningiomas demonstrate the most common intracranial primary central nervous system tumors in adults worldwide.Aim: Our purpose was to explore the role of caspase 8 expression in meningiomas' pathological features.Materials and methods: A total of 50 meningioma cases were included in the study, comprising a broad spectrum of histopathological sub-types. An immunohistochemistry assay was applied on tissue microarray cores followed by digital image analysis.Results: Overexpression of caspase 8 protein was observed in 21/50 (42%) cases, whereas the rest of them (29/50, 58%) demonstrated moderate to low levels of the molecule. Caspase 8 overall expression was statistically significantly correlated to grade of the examined tumors and to mitotic index (p=0.001, p=0.002, respectively).Conclusions: Caspase 8 aberrant expression is observed in meningiomas associated with their differentiation grade and mitotic activity. Targeted therapeutic strategies focused on enhancing caspase 8 expression and also inducing the overall apoptotic activity should be a very promising approach in rationally handling sub-groups of meningioma patients.

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High expression of anti-apoptotic genes in grade I and II meningiomas

Cited by 4 publications

References 29 publications

FLIP as a therapeutic target in cancer

FLIP as a therapeutic target in cancer

c-FLIP, a Novel Biomarker for Cancer Prognosis, Immunosuppression, Alzheimer's Disease, Chronic Obstructive Pulmonary Disease (COPD), and a Rationale Therapeutic Target

Caspase 8 Expression Patterns in Meningiomas: A Tissue Microarray Digital Image Analysis

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