TAK1 regulates endothelial cell necroptosis and tumor metastasis

Liu, Yang; Joseph, Sayali; Sun, Tianliang; Hoffmann, Júlia; Thevissen, Sophia; Offermanns, Stefan; Strilić, Boris

doi:10.1038/s41418-018-0271-8

Cited by 43 publications

(40 citation statements)

References 47 publications

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“…TAK1 deletion resulted in increased expression of RIPK3 in endothelial cells and enhanced both necroptosis of endothelial cells and metastasis of tumor cells (Yang et al, 2019). Deficiency of RIPK3 effectively inhibited tumor metastasis in epithelium-specific TAK1 knockout mice (Yang et al, 2019). These results support the idea that sustained TAK1 signaling is required for controlling the low levels of necroptosis components in endothelial cells.…”

Section: Necroptosis In the Promotion Of Metastasissupporting

confidence: 54%

“…Recently, it has been reported that endothelial TGF-β-activated kinase 1 (TAK1) acts as a negative regulator of endothelial necroptosis and metastasis (Yang et al, 2019). TAK1 deletion resulted in increased expression of RIPK3 in endothelial cells and enhanced both necroptosis of endothelial cells and metastasis of tumor cells (Yang et al, 2019). Deficiency of RIPK3 effectively inhibited tumor metastasis in epithelium-specific TAK1 knockout mice (Yang et al, 2019).…”

Section: Necroptosis In the Promotion Of Metastasismentioning

confidence: 99%

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Complex roles of necroptosis in cancer

Zhu

Zhang

Yang

et al. 2019

J. Zhejiang Univ. Sci. B

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Necroptosis is a tightly regulated form of necrosis that requires the activation of receptor-interacting protein (RIP) kinases RIPK1 and RIPK3, as well as the RIPK3 substrate mixed lineage kinase domain-like protein (MLKL). Because of membrane rupture, necroptotic cells release damage-associated molecular patterns (DAMPs) that evoke immune responses. Necroptosis is emerging as an important cellular response in the modulation of cancer initiation, progression, and metastasis. Necroptosis of cancer cells is considered to be an immunogenic cell death capable of activating anti-tumor immunity. Necroptosis also participates in the promotion of myeloid cell-induced adaptive immune suppression and thus contributes to oncogenesis. In addition, necroptosis of endothelial cells and tumor cells is conducive to tumor metastasis. In this review, we summarize the current knowledge of the complex role of necroptosis in cancer and discuss the potential of targeting necroptosis components for cancer therapies.

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Section: Necroptosis In the Promotion Of Metastasissupporting

confidence: 54%

Section: Necroptosis In the Promotion Of Metastasismentioning

confidence: 99%

Complex roles of necroptosis in cancer

Zhu

Zhang

Yang

et al. 2019

J. Zhejiang Univ. Sci. B

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“…These distinctions get further complicated if necroptosis is positioned within a tumor tissue context. For example, IL1α release from necroptotic cancer cells can stimulate the "bystander" stromal cells to proliferate thereby auto-fueling tumor progression via stroma-derived growth factors [20,217,220,251]. Similarly, necroptosis-associated release of reactive nitrogen intermediates (RNI) and/or ROS, at threshold levels, may facilitate pro-tumorigenic processes [20].…”

Section: Necroptosis-driven Modulation Of Anticancer Immunitymentioning

confidence: 99%

Necroptosis in Immuno-Oncology and Cancer Immunotherapy

Sprooten

Wijngaert

Vanmeerbeek

et al. 2020

Cells

132

112

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Immune-checkpoint blockers (ICBs) have revolutionized oncology and firmly established the subfield of immuno-oncology. Despite this renaissance, a subset of cancer patients remain unresponsive to ICBs due to widespread immuno-resistance. To “break” cancer cell-driven immuno-resistance, researchers have long floated the idea of therapeutically facilitating the immunogenicity of cancer cells by disrupting tumor-associated immuno-tolerance via conventional anticancer therapies. It is well appreciated that anticancer therapies causing immunogenic or inflammatory cell death are best positioned to productively activate anticancer immunity. A large proportion of studies have emphasized the importance of immunogenic apoptosis (i.e., immunogenic cell death or ICD); yet, it has also emerged that necroptosis, a programmed necrotic cell death pathway, can also be immunogenic. Emergence of a proficient immune profile for necroptosis has important implications for cancer because resistance to apoptosis is one of the major hallmarks of tumors. Putative immunogenic or inflammatory characteristics driven by necroptosis can be of great impact in immuno-oncology. However, as is typical for a highly complex and multi-factorial disease like cancer, a clear cause versus consensus relationship on the immunobiology of necroptosis in cancer cells has been tough to establish. In this review, we discuss the various aspects of necroptosis immunobiology with specific focus on immuno-oncology and cancer immunotherapy.

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“…Together, these results suggested that intravitreal injection of 5Z-7-oxozeaenol does not result in adverse or toxic effects on retinal function and structure up to 28 days post-injection. DISCUSSION TAK1 is a key modulator involved in a range of cellular functions including the immune response (14), cell survival and death (16), angiogenesis (20), fibrosis (30) and tumor metastasis (31). TAK1 is activated in response to various stimuli such as pro-inflammatory cytokines, hypoxia, oxidative stress, metabolism, DNA damage, Wnt and osmotic shock (14,(32)(33)(34).…”

Section: Inhibition Of Tak1 Attenuates Retinal Neovascularization In mentioning

confidence: 99%

TAK1 blockade as a therapy for retinal neovascularization

Lin

Wang

Chen

et al. 2021

Preprint

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Retinal neovascularization, or pathological angiogenesis in the retina, is a leading cause of blindness in developed countries. Pathological angiogenesis occurs through the complex activation of pro-inflammatory and pro-angiogenic pathways. Transforming growth factor-β-activated kinase 1 (TAK1) is a mitogen-activated protein kinase kinase kinase (MAPKKK) activated by TGF-β1 and other pro-inflammatory cytokines such as tumor necrosis factor α (TNFα) and interleukin-1 (IL-1). TAK1 is a key mediator of inflammation, innate immune responses, apoptosis and tissue homeostasis and plays an important role in physiological angiogenesis. Its role in pathological angiogenesis, particularly in retinal neovascularization, remains unclear. We investigated the regulatory role of TAK1 in pathological angiogenesis in the retina. Transcriptome analysis of human retina featuring retinal neovascularization revealed enrichment of known TAK1-mediated signaling pathways. Genetic or pharmacological inhibition of TAK1 activation in human endothelial cells induced by TNFα or IL-1 stimulation led to inhibition of phosphorylation of major kinases, including nuclear factor kappa B (NFκB) and mitogen-activated protein kinase (MAPK) signaling pathways. Suppression of this signaling, in turn, decreased expression of downstream genes associated with inflammation and angiogenesis, suggesting that TAK1 is required for these pathological processes. Transcriptome analysis of endothelial cells revealed that TAK1 knockout prevented inflammatory and immune responses induced by TNFα stimulation, mainly via cytokine and chemokine activity. Selective inhibition of TAK1 by 5Z-7-oxozeaenol in vitro ameliorated pro-angiogenic activity, including endothelial cell proliferation, migration and tube formation. Moreover, 5Z-7-oxozeaenol attenuated aberrant retinal angiogenesis in rats following oxygen-induced retinopathy. Our finding shows that TAK1 plays a key role in pathological angiogenesis in the retina. Selective inhibition of TAK1 prevents pathological angiogenesis, suggesting that TAK1 could be a potential therapeutic target for retinal neovascularization.GRAPHICAL ABSTRACT

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TAK1 regulates endothelial cell necroptosis and tumor metastasis

Cited by 43 publications

References 47 publications

Complex roles of necroptosis in cancer

Complex roles of necroptosis in cancer

Necroptosis in Immuno-Oncology and Cancer Immunotherapy

TAK1 blockade as a therapy for retinal neovascularization

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