Necroptosis, tumor necrosis and tumorigenesis

Liu, Zheng-gang; Jiao, Delong

doi:10.15698/cst2020.01.208

Cited by 130 publications

(104 citation statements)

References 63 publications

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“…Interestingly, tumors with necrosis had significantly lower mRNA expression levels of necroptotic molecules compared to those without necrosis. Tumor necrosis is a result of inadequate vascularization and subsequent metabolic stress such as hypoxia and nutrient deprivation [17], and it has been reported as an indicator of poor prognosis in NSCLC [19]. Our study also showed a tendency toward worse DFS in patients with necrosis ( Supplementary Figure 2).…”

Section: Discussionsupporting

confidence: 68%

“…The study by Seifert et al reported that in pancreatic ductal adenocarcinoma, the necroptotic molecules were associated with tumor promoting function associated with macrophage-induced adaptive immune suppression [15]. Recently, necroptotic cell death pathway was shown to be involved in tumor necrosis and high level of potassium released from necrotic tumor cells inhibits both CD4 and CD8 T cell activity leading to tumor development and metastasis [16,17]. Another study regarding mouse MMVT-PyMT breast tumor showed that RIPK3 expression was decreased in the early stages, but a significant increase of RIPK3 and MLKL expression was detected in late stage tumors that bear tumor necrosis, suggesting the necroptosis promotes tumor development [17,18].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, necroptotic cell death pathway was shown to be involved in tumor necrosis and high level of potassium released from necrotic tumor cells inhibits both CD4 and CD8 T cell activity leading to tumor development and metastasis [16,17]. Another study regarding mouse MMVT-PyMT breast tumor showed that RIPK3 expression was decreased in the early stages, but a significant increase of RIPK3 and MLKL expression was detected in late stage tumors that bear tumor necrosis, suggesting the necroptosis promotes tumor development [17,18]. Collectively, the results regarding the role of necroptosis in cancers are conflicting due to the pleiotropic role of necroptotic mediators, and the distinct tumor microenvironment of each type of the cancer [1].…”

Section: Discussionmentioning

confidence: 99%

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Expression of key regulatory genes in necroptosis and its effect on the prognosis in non-small cell lung cancer

Park¹,

Lee²,

Lee³

et al. 2020

J. Cancer

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Background: Accumulating evidence suggests that necroptosis, or programmed necrotic cell death, may play a significant role in cancer. We evaluated the expression of key molecules in necroptosis and their association with clinical features and prognosis in NSCLC. Methods: A total of 253 NSCLC patients (96 squamous cell carcinoma [SCC] cases and 157 adenocarcinoma [AC] cases) who underwent curative resection were included. Tumor tissues and corresponding normal tissues were investigated for relative mRNA expression levels of RIPK1, RIPK3, and MLKL. Difference in disease free survival (DFS) was analyzed according to the expression levels of these molecules in tumor tissues. Results: NSCLC tissues had significantly lower expression of RIPK1, RIPK3, and MLKL than normal tissues (P = 1 x 10-4 , P = 8 x 10-6 , and P = 4 x 10-8 , respectively). In subgroup analysis, SCCs had significantly lower RIPK1, RIPK3, and MLKL expression (P = 5 x 10-4 , P = 3 x 10-15 , P = 1 x 10-5 , respectively), and ACs had significantly lower RIPK1 and MLKL expression (P = 0.01 and P = 6 x 10-4 , respectively) than normal tissues. Low expression of RIPK1, RIPK3, and MLKL in tumors was associated with a worse DFS (HR = 1.71, P = 0.01; HR = 1.53, P = 0.04; and HR = 1.53, P = 0.04, respectively) in a multivariate analysis. In SCC, none of the RIPK1, RIPK3, and MLKL expression was significantly associated with DFS. However, in AC, low expression of RIPK1, RIPK3, and MLKL was significantly associated with worse DFS (HR = 1.67, P = 0.03; HR = 1.70, P = 0.03; and HR = 1.81, P = 0.02, respectively). Conclusions: Key regulatory genes in necroptosis, RIPK1, RIPK3, and MLKL, were downregulated in NSCLC, and their lower expression in NSCLC may be used to predict early recurrence after curative resection, especially in AC.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Expression of key regulatory genes in necroptosis and its effect on the prognosis in non-small cell lung cancer

Park¹,

Lee²,

Lee³

et al. 2020

J. Cancer

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“…Firstly, recent investigations into the pathogenesis of SFTPA1 mutations have shown that necroptosis is increased but not apoptosis [99]. For necroptosis, both tumour-promoting and tumour-suppressing effects are reported [128]. In the study of a family with an SFTPA1 mutation and evidence of necropsis, one uncle with lung cancer was reported; however, his mutation status was unknown and tumourigenesis was not studied [99,100].…”

Section: Lung Cancermentioning

confidence: 99%

Genetic disorders of the surfactant system: focus on adult disease

2021

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Genes involved in the production of pulmonary surfactant are crucial for the development and maintenance of healthy lungs. Germline mutations in surfactant-related genes cause a spectrum of severe monogenic pulmonary diseases in patients of all ages. The majority of affected patients present at a very young age, however, a considerable portion of patients have adult-onset disease. Mutations in surfactant-related genes are present in up to 8% of adult patients with familial interstitial lung disease (ILD) and associate with the development of pulmonary fibrosis and lung cancer.High disease penetrance and variable expressivity underscore the potential value of genetic analysis for diagnostic purposes. However, scarce genotype–phenotype correlations and insufficient knowledge of mutation-specific pathogenic processes hamper the development of mutation-specific treatment options.This article describes the genetic origin of surfactant-related lung disease and presents spectra for gene, age, sex and pulmonary phenotype of adult carriers of germline mutations in surfactant-related genes.

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“…RIPK1 associates with TRIF via the RHIM domain upon TLR3 and TLR4 activation [ 10 , 25 , 26 ]. With its DD at the C-terminal, RIPK1 can be activated by several death receptors such as TNFR1, Fas, TRAILR1, and TRAILR2 [ 20 ].…”

Section: Ripks Familymentioning

confidence: 99%

The Role of Necroptosis: Biological Relevance and Its Involvement in Cancer

Torre

Nebbioso

Stunnenberg

et al. 2021

Cancers

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Regulated cell death mechanisms are essential for the maintenance of cellular homeostasis. Evasion of cell death is one of the most important hallmarks of cancer. Necroptosis is a caspase independent form of regulated cell death, investigated as a novel therapeutic strategy to eradicate apoptosis resistant cancer cells. The process can be triggered by a variety of stimuli and is controlled by the activation of RIP kinases family as well as MLKL. The well-studied executor, RIPK1, is able to modulate key cellular events through the interaction with several proteins, acting as strategic crossroads of several molecular pathways. Little evidence is reported about its involvement in tumorigenesis. In this review, we summarize current studies on the biological relevance of necroptosis, its contradictory role in cancer and its function in cell fate control. Targeting necroptosis might be a novel therapeutic intervention strategy in anticancer therapies as a pharmacologically controllable event.

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Necroptosis, tumor necrosis and tumorigenesis

Cited by 130 publications

References 63 publications

Expression of key regulatory genes in necroptosis and its effect on the prognosis in non-small cell lung cancer

Expression of key regulatory genes in necroptosis and its effect on the prognosis in non-small cell lung cancer

Genetic disorders of the surfactant system: focus on adult disease

The Role of Necroptosis: Biological Relevance and Its Involvement in Cancer

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