A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development

Boege, Yannick; Malehmir, Mohsen; Healy, Marc E.; Bettermann, Kira; Lorentzen, Anna; Vucur, Mihael; Ahuja, Akshay K.; Böhm, Friederike; Mertens, Joachim C.; Shimizu, Yutaka; Frick, Lukas; Remouchamps, Caroline; Mutreja, Karun; Kähne, Thilo; Sundaravinayagam, Devakumar; Wolf, Monika; Rehrauer, Hubert; Koppe, Christiane; Speicher, Tobias; Padrissa-Altés, Susagna; Maire, Renaud; Schattenberg, Jörn M.; Jeong, Juseong; Liu, Lei; Zwirner, Stefan; Boger, Regina; Hüser, Norbert; Davis, Roger J.; Müllhaupt, Beat; Moch, Holger; Schulze‐Bergkamen, Henning; Clavien, Pierre‐Alain; Werner, Sabine; Borsig, Lubor; Luther, Sanjiv A.; Jost, Philipp J.; Weinlich, Ricardo; Unger, Kristian; Behrens, Axel; Hillert, Laura K.; Dillon, Christopher P.; Virgilio, Michela Di; Wallach, David; Dejardin, Emmanuel; Zender, Lars; Naumann, Michael; Walczak, Henning; Green, Douglas R.; Lopes, Massimo; Lavrik, Inna N.; Luedde, Tom; Heikenwälder, Mathias; Weber, Achim

doi:10.1016/j.ccell.2017.08.010

Cited by 139 publications

(117 citation statements)

References 49 publications

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“…The penetration ability of the Fe II Àpolypyridyl complexes into U87 spheroids was performed according to al iterature procedure. [33] Briefly,t he U87 spheroids were grown for 5days. Then, the metal- based complex (35 mm)w as added and the sample was incubated for 12 h. Finally,t he sample was examined by confocal laser scanning microscopy (Zeiss LSM700).…”

Section: Transport Of the Fe II àPolypyridyl Compounds Across The Outmentioning

confidence: 99%

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Iron(II)−Polypyridyl Complexes Inhibit the Growth of Glioblastoma Tumor and Enhance TRAIL‐Induced Cell Apoptosis

Lin

Wang

Lai

et al. 2018

Chemistry An Asian Journal

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A promising cancer-targeting agent for the induction of apoptosis in tumor necrosis factor (TNF) proteins, the TNF-related apoptosis-inducing ligand (TRAIL) ligand, has found limited applications in the treatment of cancer cells, owing to its resistance by cancer cell lines. Therefore, the rational design of anticancer agents that could sensitize cancer cells towards TRAIL is of great significance. Herein, we report that synthetic iron(II)-polypyridyl complexes are capable of inhibiting the proliferation of glioblastoma cancer cells and efficiently enhancing TRAIL-induced cell apoptosis. Mechanistic studies demonstrated that the synthesized complexes induced cancer-cell apoptosis through triggering the activation of p38 and p53 and inhibiting the activation of ERK. Moreover, uPA and MMP-2/MMP-9, among the most important metastatic regulatory proteins, were also found to be significantly alerted after the treatment. Furthermore, we also found that tumor growth in nude mice was significantly inhibited by iron complex Fe2 through the induction of apoptosis without clear systematic toxicity, as indicated by histological analysis. Taken together, this study provides evidence for the further development of metal-based anticancer agents and chemosensitizers of TRAIL for the treatment of human glioblastoma cancer cells.

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Section: Transport Of the Fe II àPolypyridyl Compounds Across The Outmentioning

confidence: 99%

“…The cell-cycle distribution for cells that had been treated with the Fe II Àpolypyridyl complexes and TRAIL was determined by using a flow cytometry assay.T he proportion of sub-G1 peaks was used to quantify the cell apoptosis. [33]…”

Section: Flow Cytometrymentioning

confidence: 99%

Iron(II)−Polypyridyl Complexes Inhibit the Growth of Glioblastoma Tumor and Enhance TRAIL‐Induced Cell Apoptosis

Lin

Wang

Lai

et al. 2018

Chemistry An Asian Journal

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“…Furthermore, 70–90% of primary liver cancer cases comprise hepatocellular carcinoma (HCC) . The incidence rate in HCC is the fastest growing type of cancer in the world . At present, the main treatment for HCC is surgical operation .…”

Section: Introductionmentioning

confidence: 99%

“…2 The incidence rate in HCC is the fastest growing type of cancer in the world. 3 At present, the main treatment for HCC is surgical operation. 4 In past decades, the prognosis of patients with HCC has not been significantly improved because of a lack of obvious clinical symptoms during the early stages, which results in many patients being diagnosed when tumors have developed to the middle and late stages, at which point the opportunity for surgical resection has been missed.…”

Section: Introductionmentioning

confidence: 99%

Expression, immune infiltration and clinical significance of SPAG5 in hepatocellular carcinoma: A gene expression‐based study

Chen

et al. 2020

The Journal of Gene Medicine

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Background Overexpression of sperm‐associated antigen 5 (SPAG5) is a marker of poor prognosis in numerous tumors and is recognized as an index of tumor proliferation; however, its expression in liver cancer remains unclear. Methods The Oncomine (https://www.oncomine.org) and Timer (https://cistrome.shinyapps.io/timer) databases were used to analyze the expression of SPAG5 in liver hepatocellular carcinoma (HCC) and normal liver tissues. The relationship between the expression of SPAG5 and immune infiltration of HCC was investigated using the Timer and GEPIA (http://gepia.cancer‐pku.cn) databases, and the mechanism was analyzed using Gene Set Enrichment Analysis. A Kaplan–Meier Plotter (http://kmplot.com/analysis) was used to evaluate the effect of SPAG5 on the prognosis of patients with HCC. Results The results revealed that the SPAG5 expression level was positively correlated with the infiltration levels of CD8+ T cells, macrophages, neutrophils, and especially B cells and dendritic cells. In addition, SPAG5 expression was significantly associated with T cell exhaustion. The overall survival time, progression‐free survival time, recurrence‐free survival time and disease‐specific survival time were significantly reduced for HCC patients with high SPAG5 expression (p < 0.01) and high expression of SPAG5 was significantly associated with a poor overall survival time and progression‐free survival time of grade and stage II–III HCC (p < 0.05) but not with stage I HCC (p > 0.05). Additionally, the expression of SPAG5 is related to the p53 and cell cycle signal pathways. Conclusions In conclusion, SPAG5 is not only a marker of immune infiltration and poor prognosis, but also a potential therapeutic target for liver cancer.

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“…regulate cell death-independent processes such as cell migration (14,15), or proliferation (16) and to act as DNA-damage sensor induced by cell proliferation (17).…”

mentioning

confidence: 99%

Caspase-8 Modulates Angiogenesis By Regulating A Cell Death Independent Pathway In Endothelial Cells

Tisch

Freire-Valls

Yerbes

et al. 2019

Preprint

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During developmental angiogenesis blood vessels grow and remodel to ultimately build a hierarchical vascular network. Whether and how cell death signaling molecules contribute to blood vessel formation is still not well understood. Caspase-8 (Casp-8), a key protease in the extrinsic cell death-signaling pathway, regulates both cell death via apoptosis and necroptosis. Here we show that expression of Casp-8 in endothelial cells (ECs) is required for proper postnatal angiogenesis. EC specific Casp-8 knockout pups (Casp-8 ECko ) have reduced retinal angiogenesis, as the loss of Casp-8 reduced EC proliferation, sprouting and migration independent of its cell death function. Instead, the loss of Casp-8 caused hyperactivation of p38 mitogen-activated protein kinase (MAPK) downstream of receptorinteracting serine/threonine-protein kinase 3 (RIPK3) and destabilization of VE-cadherin at EC

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A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development

Cited by 139 publications

References 49 publications

Iron(II)−Polypyridyl Complexes Inhibit the Growth of Glioblastoma Tumor and Enhance TRAIL‐Induced Cell Apoptosis

Iron(II)−Polypyridyl Complexes Inhibit the Growth of Glioblastoma Tumor and Enhance TRAIL‐Induced Cell Apoptosis

Expression, immune infiltration and clinical significance of SPAG5 in hepatocellular carcinoma: A gene expression‐based study

Caspase-8 Modulates Angiogenesis By Regulating A Cell Death Independent Pathway In Endothelial Cells

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