A decade of cell death studies: Breathing new life into necroptosis

Khan, Imran; Yousif, Abdelrahman; Chesnokov, Mikhail S.; Hong, Linda; Chefetz, IIana I.

doi:10.1016/j.pharmthera.2020.107717

Cited by 84 publications

(56 citation statements)

References 174 publications

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“…Regulated cell death (RCD) is an autonomous and orderly death. In addition to apoptosis and necroptosis, recent studies have revealed new modes of RCD, including pyroptosis and ferroptosis [ 5 , 6 , 7 , 8 ]. All of these death modes present distinct features in terms of cellular morphology, biochemistry, and signaling pathways ( Table 1 ).…”

Section: Introductionmentioning

confidence: 99%

“…Receptor-interacting protein kinase 1 (RIPK1), RIPK3 and the mixed lineage kinase domain-like pseudokinase (MLKL) are required proteins for the activation of necroptosis. In response to death receptor activation, the binding of RIPK1 to RIPK3 triggers the formation of necrosomes, resulting in MLKL activation [ 8 ]. As a necroptotic effector, the activated MLKL translocates to the plasma membrane, causing permeabilization and subsequent cell death.…”

Section: Introductionmentioning

confidence: 99%

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The Evolving Role of Ferroptosis in Breast Cancer: Translational Implications Present and Future

Lin

Chang

et al. 2021

Cancers

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Breast cancer (BC) is the most common malignancy among women worldwide. The discovery of regulated cell death processes has enabled advances in the treatment of BC. In the past decade, ferroptosis, a new form of iron-dependent regulated cell death caused by excessive lipid peroxidation has been implicated in the development and therapeutic responses of BC. Intriguingly, the induction of ferroptosis acts to suppress conventional therapy-resistant cells, and to potentiate the effects of immunotherapy. As such, pharmacological or genetic modulation targeting ferroptosis holds great potential for the treatment of drug-resistant cancers. In this review, we present a critical analysis of the current understanding of the molecular mechanisms and regulatory networks involved in ferroptosis, the potential physiological functions of ferroptosis in tumor suppression, its potential in therapeutic targeting, and explore recent advances in the development of therapeutic strategies for BC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Evolving Role of Ferroptosis in Breast Cancer: Translational Implications Present and Future

Lin

Chang

et al. 2021

Cancers

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“…Recently, necrosis has been found to not be absolutely unregulated, which was called “necroptosis.” 6 Under apoptosis‐deficient conditions, such as the inactivation of caspase 8 or the loss of its adaptor Fas‐associated protein with death domain (FADD) 7 or treatment with pancaspase inhibitors, necroptosis could be activated to execute cell death as an alternative mode of cell death 8 . In contrast to apoptosis, which is mediated by the cascade activation of caspases, necroptosis critically requires the activation of receptor‐interacting serine‐threonine protein kinase 1 (RIP1), RIP3, and mixed lineage kinase domain‐like (MLKL) 6 . In brief, following the induction of necroptosis by various stimuli, activated RIP1 interacts with RIP3 to form a complex called the “necrosome.” 9 Subsequently, autophosphorylated RIP3 recruits and phosphorylates MLKL, causing the oligomerization and activation of MLKL 10 .…”

Section: Introductionmentioning

confidence: 99%

Connexin32 activates necroptosis through Src‐mediated inhibition of caspase 8 in hepatocellular carcinoma

et al. 2021

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Necroptosis is an alternative form of programmed cell death that generally occurs under apoptosis‐deficient conditions. Our previous work showed that connexin32 (Cx32) promotes the malignant progress of hepatocellular carcinoma (HCC) by enhancing the ability of resisting apoptosis in vivo and in vitro. Whether triggering necroptosis is a promising strategy to eliminate the apoptosis‐resistant HCC cells with high Cx32 expression remains unknown. In this study, we found that Cx32 expression was positively correlated with the expression of necroptosis protein biomarkers in human HCC specimens, cell lines, and a xenograft model. Treatment with shikonin, a well‐used necroptosis inducer, markedly caused necroptosis in HCC cells. Interestingly, overexpressed Cx32 exacerbated shikonin‐induced necroptosis, but downregulation of Cx32 alleviated necroptosis in vitro and in vivo. Mechanistically, Cx32 was found to bind to Src and promote Src‐mediated caspase 8 phosphorylation and inactivation, which ultimately reduced the activated caspase 8‐mediated proteolysis of receptor‐interacting serine‐threonine protein kinase 1/3, the key molecule for necroptosis activation. In conclusion, we showed that Cx32 contributed to the activation of necroptosis in HCC cells through binding to Src and then mediating the inactivation of caspase 8. The present study suggested that necroptosis inducers could be more favorable than apoptosis inducers to eliminate HCC cells with high expression of Cx32.

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“…It is known that the process of division, proliferation, differentiation and survival of cells is the basis of life of all living beings (Elliott & Ravichandran, 2016;Papayannopoulos, 2018;Cahilog et al, 2020). Over time, scientists became interested in the mechanisms of regulation of cell division, aging and cell death (Jorgensen et al, 2017;Kambara et al, 2018;Khan et al, 2021). Recently, more and more information is emerging in sources about the physiology of cells, and especially about the regulation of division, aging and death.…”

Section: Introductionmentioning

confidence: 99%

Сell death and its significance in reproductive pathology

Zhelavskyi

Kernychnyi

Dmytriv

2021

Ukr. Jour. of Vet. and Agr. Sci.

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Since the middle of the last century, scientists have been interested in the mechanisms of regulation of cell division, differentiation and aging of cells. The first objects of study were insects, helminths and other living organisms. From the very beginning, in the biology of cell development and regulation, scientists have attached leading importance to genetic factors. Later, more and more experience was gained on the influence of intracellular factors, metabolic changes and exogenous pathogens on the programmed cell death. Recent research on cell biology and pathology has focused on the study of apoptosis. The first described phenomenon of programmed cell death was apoptosis. Subsequent studies were aimed at the study programmed cell death. This review will provide an opportunity to consider the biological mechanisms of programmed cell death, differences and species characteristics. The author described the clinical aspects of apoptosis, necroptosis and pyroptosis and their importance in the formation of cellular homeostasis. In the present review article simple classification system, where the cell death entities are primarily categorized into programmed cell death. Multiple mechanisms and phenotypes compose programmed non-apoptotic cell death, including: autophagy, entosis, methuosis and paraptosis, mitoptosis and parthanatos, ferroptosis, pyroptosis NETosis and necroptosis. Changes of cellular regulation at development of pathologies at people and animals are considered. Cell biology includes a variety of mechanisms of programmed aging and death. Modern research is aimed at deepening the study multiple mechanisms and phenotypes compose programmed. Cells. will certainly be taken into account by the Nomenclature Committee on Cell Death. Cellular regulation is associated with a variety of physiological mechanisms of development, and is also important in processes such as inflammation, immune response, embryogenesis maintenance of tissue homeostasis. Study of factors of influence and mechanisms of regulation of aging of cells opens a curtain for development of the newest means of diagnostics of pathologies and development of pharmacological means for correction of cellular mechanisms at development of pathologies.

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A decade of cell death studies: Breathing new life into necroptosis

Cited by 84 publications

References 174 publications

The Evolving Role of Ferroptosis in Breast Cancer: Translational Implications Present and Future

The Evolving Role of Ferroptosis in Breast Cancer: Translational Implications Present and Future

Connexin32 activates necroptosis through Src‐mediated inhibition of caspase 8 in hepatocellular carcinoma

Сell death and its significance in reproductive pathology

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