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

Safa, Ahmad R.; Kamocki, Krzysztof; Saadatzadeh, M. Reza; Bijangi-Vishehsaraei, Khadijeh

doi:10.36648/2472-1646.5.1.59

Cited by 7 publications

(6 citation statements)

References 127 publications

(237 reference statements)

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“…125 ). Moreover, malignancies exhibiting high CFLAR levels or reduced expression of RIPK3 and mixed lineage kinase domain like pseudokinase (MLKL, another component of the necroptotic apparatus) exhibit poor prognosis linked to deficient immunosurveillance 141,142 . Similar strategies are also employed by intracellular bacteria.…”

Section: Subversion Of Icd By Viruses and Cancer Cellsmentioning

confidence: 99%

Immunogenic cell stress and death

et al. 2022

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Section: Subversion Of Icd By Viruses and Cancer Cellsmentioning

confidence: 99%

Immunogenic cell stress and death

et al. 2022

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“…Interestingly, cFLIP downregulation in colon cancer cells showed to upregulate TRAIL-R2 expression, suggesting the possibility of cFLIP on the activation of TRAIL death pathway [ 50 ]. Moreover, the involvement of cFLIP in the resistance of Fas-mediated apoptosis has been reported in several cancers, including CCA [ 18 , 51 , 52 ]. Treatment of Fas agonist failed to promote cancer cell death in highly expressed cFLIP lymphoma (Karpas 299 and SU-DHL1), which could be sensitized by using cFLIP RNA interference [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Genistein Sensitizes Human Cholangiocarcinoma Cell Lines to Be Susceptible to Natural Killer Cells

Chiawpanit

Panwong

Sawasdee

et al. 2022

Biology

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Cholangiocarcinoma (CCA) is a lethal bile duct cancer, which has poor treatment outcomes due to its high resistance to chemotherapy and cancer recurrence. Activation of aberrant anti-apoptotic signaling pathway has been reported to be a mechanism of chemoresistance and immune escape of CCA. Therefore, reversal of anti-apoptotic signaling pathway represents a feasible approach to potentiate effective treatments, especially for CCA with high chemoresistance. In this study, we demonstrated the effects of genistein on reactivation of apoptosis cascade and increase the susceptibility of CCA cells to natural killer (NK-92) cells. Genistein at 50 and 100 µM significantly activated extrinsic apoptotic pathway in CCA cells (KKU055, KKU100, and KKU213A), which was evident by reduction of procaspase-8 and -3 expression. Pretreatment of CCA cells with genistein at 50 µM, but not NK-92 cells, significantly increased NK-92 cell killing ability over the untreated control, suggesting the ability of genistein to sensitize CCA cells. Interestingly, genistein treatment could greatly lower the expression of cFLIP, an anti-apoptotic protein involved in the immune escape pathway, in addition to upregulation of death receptors, Fas- and TRAIL-receptors, in CCA cells, which might be the underlying molecular mechanism of genistein to sensitize CCA to be susceptible to NK-92 cells. Taken together, this finding revealed the benefit of genistein as a sensitizer to enhance the efficiency of NK cell immunotherapy for CCA.

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“…The CaMKII-mediated pathway for CFLAR (c-FLIP) upregulation protects melanoma cells from TRAILinduced apoptosis [33]. 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 [34]. CFLAR (c-FLIP) also played important role on melanomas [35,36].…”

Section: Discussionmentioning

confidence: 99%

Correlation of Autophagy-Related Genes in High Risk and Low Risk Signatures Based on Prognostic Index Model SKCM Patient

Zhang¹,

Liang²,

Tian³

et al. 2021

Preprint

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Autophagy plays a dual role in tumor development and autophagy-related genes (ARGs) involved in the development of cancer. However, the correlation between these high and low risk ARGs is still unclear. To systematically study the relationship between ARGs and melanoma patients, the expression profiles of ARGs were integratedly analyzed based on the TCGA and GTEx dataset. The results suggested 8-ARGs marker can predict the prognosis of skin cutaneous melanoma (SKCM), 5-ARGs (CFLAR, DAPK2, ITGA6, DNAJB9 and RGS19) were low risk index, 3-ARGs (EIF2AK2, EGFR and PTK6) were high risk index. Further validation showed CFLAR, DNAJB9 and PTK6 were significant related to SKCM. In tumor immunization, CFLAR and DNAJB9 have stronger correlation with tumor immune cells, and there is a significant positive correlation among the low risk genes. However, there is no significant correlation between the high and low risk factors. In addition, our results also showed that CFLAR and PTK6 were significantly negatively correlated with tumor purity; PTK6 was significantly positively correlated with patient's age, CFLAR was significantly negatively correlated with patient's age; CFLAR and DNAJB9 were significantly positively correlated in purity and age. It provides a new prognostic indicator for patients and a new idea for the mechanism of autophagy in melanoma.

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

Cited by 7 publications

References 127 publications

Immunogenic cell stress and death

Immunogenic cell stress and death

Genistein Sensitizes Human Cholangiocarcinoma Cell Lines to Be Susceptible to Natural Killer Cells

Correlation of Autophagy-Related Genes in High Risk and Low Risk Signatures Based on Prognostic Index Model SKCM Patient

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