c-FLIP, a Novel Biomarker for Cancer Prognosis, Immunosuppression, Alzheimer's Disease, Chronic Obstructive Pulmonary Disease (COPD), and a Rationale Therapeutic Target
| Autor: | Khadijeh Bijangi-Vishehsaraei, Ahmad R. Safa, Krzysztof Kamocki, M. Reza Saadatzadeh |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Programmed cell death
c-FLIP Necroptosis Death receptor pathways Apoptosis Disease 030204 cardiovascular system & hematology Article 03 medical and health sciences 0302 clinical medicine Medicine FADD Antiapoptotic proteins Death domain Cancer biomarker biology business.industry Cancer Cytokine resistance medicine.disease Biomarker (cell) Drug resistance 030220 oncology & carcinogenesis Cancer cell biology.protein Cancer research business |
| Zdroj: | Biomarkers journal |
| DOI: | 10.36648/2472-1646.5.1.59 |
| Popis: | 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-FLIPL) and short (c-FLIPS) 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. |
| Databáze: | OpenAIRE |
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