Relevance of necroptosis in cancer

Lalaoui, Najoua; Brumatti, Gabriela

doi:10.1038/icb.2016.120

Cited by 47 publications

(53 citation statements)

References 104 publications

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“…Tumor necrosis was often observed in the core regions of solid tumors that had reached a certain size as seen in the MMVT-PyMT breast tumor (Supplementary information, Figure S1a). 9 Although necroptotic pathway has been reported involved in tumor development, 8 it is unclear whether tumor cells undergo necroptosis during tumor progression, and whether necroptosis plays any role in tumor necrosis. To explore the potential involvement of necroptosis in tumor necrosis, we first examined the expression of MLKL protein and its phosphorylation status, which is the hallmark of activated necroptosis, 3,4 in different MMVT-PyMT breast tumor samples by immunohistochemistry.…”

Section: Dear Editormentioning

confidence: 99%

Necroptosis of tumor cells leads to tumor necrosis and promotes tumor metastasis

et al. 2018

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Section: Dear Editormentioning

confidence: 99%

Necroptosis of tumor cells leads to tumor necrosis and promotes tumor metastasis

et al. 2018

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“…However, when NF-κB or its regulators are blocked (for example, by cIAP inhibition), deubiquitylation of RIPK1 happens, which induces its release and the formation of other complexes that favor CD. Notably, the deubiquitylation of RIPK1 can also be directly promoted by drugs, such as the so-called second mitochondrial activator of caspases (Smac) mimetics [23]. The association of Fas-associated protein with the death domain (FADD), TRADD, FLICE-inhibitory protein (FLIP), and pro-caspase-8 forms cytosolic complex IIa, and the activation of pro-caspase-8 into caspase-8, promotes RIPK1-independent apoptosis [4,18].…”

Section: Figurementioning

confidence: 99%

Necroptosis in Cholangiocarcinoma

Sarcognato

Jong

Fabris

et al. 2020

Cells

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Necroptosis is a type of regulated cell death that is increasingly being recognized as a relevant pathway in different pathological conditions. Necroptosis can occur in response to multiple stimuli, is triggered by the activation of death receptors, and is regulated by receptor-interacting protein kinases 1 and 3 and mixed-lineage kinase domain-like, which form a regulatory complex called the necrosome. Accumulating evidence suggests that necroptosis plays a complex role in cancer, which is likely context-dependent and can vary among different types of neoplasms. Necroptosis serves as an alternative mode of programmed cell death overcoming apoptosis and, as a pro-inflammatory death type, it may inhibit tumor progression by releasing damage-associated molecular patterns to elicit robust cross-priming of anti-tumor CD8+ T cells. The development of therapeutic strategies triggering necroptosis shows great potential for anti-cancer therapy. In this review, we summarize the current knowledge on necroptosis and its role in liver biliary neoplasms, underlying the potential of targeting necroptosis components for cancer treatment.Cells 2020, 9, 982 2 of 18 (RIPK3) and mixed lineage kinase domain-like (MLKL) [4]. Therefore, necroptosis is an alternative mode of CD when the caspase-8-dependent apoptotic pathway is blocked. It is now well-established that various stimuli can initiate necroptosis, including intra-and extracellular factors, such as tumor necrosis factor α (TNFα) and reactive oxygen species (ROS) [5].A hallmark of cancer is the ability of malignant cells to evade apoptosis. Therefore, the induction of necroptosis could be an alternative strategy for killing cancer cells. Several therapeutics able to affect the necroptotic cascade have recently been developed, and a few of them are already in phase 1 trials for the treatment of inflammatory diseases. Moreover, necroptosis modulation is becoming the target of several new anti-cancer strategies. In fact, it has been demonstrated that apoptosis-resistant tumors respond to necroptosis, and that necroptosis can create an immunogenic microenvironment that enhances tumor clearance [6]. These aspects will be further discussed in the following chapters.Herein, we will discuss the general aspects of necroptosis and what is currently known on its involvement in cholangiocarcinoma (CCA), in order to provide perspectives for future studies in this relatively new field. Overview on Types of Cell DeathIn 2005, the Nomenclature Committee on Cell Death (NCCD) defined the first CD classification purely based on morphological criteria. This classification included three major forms of CD: types I, II, and III [7]. Type I CD, termed apoptosis, exhibits cell shrinkage, membrane blebbing, DNA fragmentation, chromatin condensation, and the formation of apoptotic bodies. Apoptosis is a form of RCD and responds to two different death signals: damage from inside the cell, such as DNA damage, which elicits an intrinsic pathway, and extracellular stimuli, such as TNFα and the Fas ligand, ...

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“…It further stresses the paradoxical role of inflammation in the context of tumor immunity: although the established tumor microenvironment is typically viewed as immunosuppressive, proinflammatory signals are strongly implicated at various points during tumorigenesis and metastasis [92]. Therefore, it is likely that the specific combination of inflammatory signals derived from necroptotic cells, and the role they play in either promoting or suppressing antitumor immune responses, will prove to be context-specific [93][94][95][96][97]. We stress an outstanding need for thorough characterization of downstream RIPK3 signaling effects across different cell types, and across diverse categories of neoplasia, in consideration of whether immunogenic PCD such as necroptosis could confer an overall therapeutic benefit to the patient.…”

Section: Roles For Necroptosis During Oncogenesismentioning

confidence: 99%

Comparing the effects of different cell death programs in tumor progression and immunotherapy

2018

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Our conception of programmed cell death has expanded beyond apoptosis to encompass additional forms of cell suicide, including necroptosis and pyroptosis; these cell death modalities are notable for their diverse and emerging roles in engaging the immune system. Concurrently, treatments that activate the immune system to combat cancer have achieved remarkable success in the clinic. These two scientific narratives converge to provide new perspectives on the role of programmed cell death in cancer therapy. This review focuses on our current understanding of the relationship between apoptosis and antitumor immune responses and the emerging evidence that induction of alternate death pathways such as necroptosis could improve therapeutic outcomes. • Can inflammatory forms of tumor cell death be used as a novel type of prophylactic tumor vaccination for tumors with conserved antigens? • Will maximizing the immunogenicity of tumor cell death synergize with emerging immunotherapies, such as immune checkpoint blockade?

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Relevance of necroptosis in cancer

Cited by 47 publications

References 104 publications

Necroptosis of tumor cells leads to tumor necrosis and promotes tumor metastasis

Necroptosis of tumor cells leads to tumor necrosis and promotes tumor metastasis

Necroptosis in Cholangiocarcinoma

Comparing the effects of different cell death programs in tumor progression and immunotherapy

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