Abstract:
:Caspase-8 was originally identified as a central player of programmed cell death triggered by death receptor stimulation. In that context, its activity is tightly regulated through several mechanisms, with the best established being the expression of FLICE-like inhibitory protein (FLIP) family proteins and the Src-dependent phosphorylation of Caspase-8 on Tyr380. Loss of apoptotic signaling is a hallmark of cancer and indeed Caspase-8 expression is often lost in tumors. This event may account not only for cancer progression but also for cancer resistance to radiotherapy and chemotherapy. Intriguingly, other tumors, such as glioblastoma, preferentially retain Caspase-8 expression, and high levels of Caspase-8 expression may correlate with a worse prognosis, suggesting that in this context this protease loses its apoptotic activity and gains additional functions. Using different cellular systems, it has been clearly shown that in cancer Caspase-8 can exhibit non-canonical functions, including promotion of cell adhesion, migration, and DNA repair. Intriguingly, in glioblastoma models, Caspase-8 can promote NF-κB-dependent expression of several cytokines, angiogenesis, and in vitro and in vivo tumorigenesis. Overall, these observations suggest that some cancer cells may hijack Caspase-8 function which in turn promote cancer progression and resistance to therapy. Here we aim to highlight the multiple functions of Caspase-8 and to discuss whether the molecular mechanisms that modulate the balance between those functions may be targeted to dismantle the aberrant activity of Caspase-8 and to restore its canonical apoptotic functionality.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Fianco G,Contadini C,Ferri A,Cirotti C,Stagni V,Barilà Ddoi
10.3390/ijms19123798subject
Has Abstractpub_date
2018-11-29 00:00:00issue
12issn
1422-0067pii
ijms19123798journal_volume
19pub_type
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journal_title:International journal of molecular sciences
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更新日期:2018-08-27 00:00:00
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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abstract::The role of Hedgehog (Hh) signaling in vascular biology has first been highlighted in embryos by Pepicelli et al. in 1998 and Rowitch et al. in 1999. Since then, the proangiogenic role of the Hh ligands has been confirmed in adults, especially under pathologic conditions. More recently, the Hh signaling has been propo...
journal_title:International journal of molecular sciences
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更新日期:2019-06-24 00:00:00
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journal_title:International journal of molecular sciences
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doi:10.3390/ijms18061182
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journal_title:International journal of molecular sciences
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doi:10.3390/ijms20030580
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abstract::Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted great attention in many biomedical fields and are used in preclinical/experimental drug delivery, hyperthermia and medical imaging. In this study, biocompatible magnetite drug carriers, stabilized by a dextran shell, were developed to carry tissue plas...
journal_title:International journal of molecular sciences
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doi:10.3390/ijms18091837
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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doi:10.3390/ijms17121973
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
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abstract::Kabuki syndrome (KS) is a rare disorder characterized by multiple congenital anomalies and variable intellectual disability caused by mutations in KMT2D/MLL2 and KDM6A/UTX, two interacting chromatin modifier responsible respectively for 56-75% and 5-8% of the cases. To date, three KS patients with mosaic KMT2D deletio...
journal_title:International journal of molecular sciences
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abstract::Parkinson's disease (PD) is characterized by distinct motor and non-motor symptoms. Sleep disorders are the most frequent and challenging non-motor symptoms in PD patients, and there is growing evidence that they are a consequence of disruptions within the circadian system. PD is characterized by a progressive degener...
journal_title:International journal of molecular sciences
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更新日期:2018-06-03 00:00:00
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journal_title:International journal of molecular sciences
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journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
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