Notch Signaling and Liver Cancer

Kawaguchi, Kazunori; Kaneko, Shuichi

doi:10.1007/978-3-030-55031-8_6

Cited by 25 publications

(9 citation statements)

References 76 publications

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“…In the physiological state, notch signaling pathway has important role in regulating proliferation, differentiation, cell-fate determination and self-renewal of stem and progenitor cell [ 86 – 88 ]. In the pathological state, the deregulation of notch signaling pathway has been demonstrated in a variety of tumors containing PCa and is associated with tumorigenesis and progression [ 89 – 93 ]. These results strongly support our findings.…”

Section: Discussionmentioning

confidence: 99%

Membrane tension-mediated stiff and soft tumor subtypes closely associated with prognosis for prostate cancer patients

Wang

Shi

et al. 2023

Eur J Med Res

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Background Prostate cancer (PCa) is usually considered as cold tumor. Malignancy is associated with cell mechanic changes that contribute to extensive cell deformation required for metastatic dissemination. Thus, we established stiff and soft tumor subtypes for PCa patients from perspective of membrane tension. Methods Nonnegative matrix factorization algorithm was used to identify molecular subtypes. We completed analyses using software R 3.6.3 and its suitable packages. Results We constructed stiff and soft tumor subtypes using eight membrane tension-related genes through lasso regression and nonnegative matrix factorization analyses. We found that patients in stiff subtype were more prone to biochemical recurrence than those in soft subtype (HR 16.18; p < 0.001), which was externally validated in other three cohorts. The top ten mutation genes between stiff and soft subtypes were DNAH, NYNRIN, PTCHD4, WNK1, ARFGEF1, HRAS, ARHGEF2, MYOM1, ITGB6 and CPS1. E2F targets, base excision repair and notch signaling pathway were highly enriched in stiff subtype. Stiff subtype had significantly higher TMB and T cells follicular helper levels than soft subtype, as well as CTLA4, CD276, CD47 and TNFRSF25. Conclusions From the perspective of cell membrane tension, we found that stiff and soft tumor subtypes were closely associated with BCR-free survival for PCa patients, which might be important for the future research in the field of PCa.

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Section: Discussionmentioning

confidence: 99%

Membrane tension-mediated stiff and soft tumor subtypes closely associated with prognosis for prostate cancer patients

Wang

Shi

et al. 2023

Eur J Med Res

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“…Increased intracellular reactive oxygen species (ROS) levels have a huge impact on biological systems. it has been shown that interactions between hepatocytes are closely regulated by Notch signaling, which is associated with bile duct dysplasia in Alagille syndrome, caused by mutations in the Jagged1 gene (Kawaguchi & Kaneko, 2021). Notch and hepatocarcinogenesis are closely linked, as cancer signaling is influenced by hepatocyte and cancer stem cell development.…”

Section: Discussionmentioning

confidence: 99%

Roxadustat induces hepatotoxicity in zebrafish embryos via inhibiting Notch signaling

Yang

Xiao

Wan

et al. 2023

J of Applied Toxicology

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Roxadustat is a novel and effective small‐molecule inhibitor of hypoxia‐inducible factor prolyl hydroxylase (HIF‐PHI). However, little research has been done on its toxicity to vertebrate embryonic development. In this study, we used zebrafish to assess the effects of roxadustat on early embryonic development. Exposure to 14, 28, and 56 μM roxadustat resulted in abnormal embryonic development in zebrafish embryos, such as shortened body length and early liver developmental deficiency. Roxadustat exposure resulted in liver metabolic imbalance and abnormal liver tissue structure in adult zebrafish. In addition, roxadustat could up‐regulate oxidative stress, and astaxanthin (AS) could partially rescue liver developmental defects by down‐regulation of oxidative stress. After exposure to roxadustat, the Notch signaling is down‐regulated, and the use of an activator of Notch signaling can partially rescue hepatotoxicity. Therefore, our research indicates that roxadustat may induce zebrafish hepatotoxicity by down‐regulating Notch signaling. This study provides a reference for the clinical use of roxadustat.

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“…Notch signaling pathway is closely related to the dysregulation of HCC cell apoptosis in the occurrence and development of HCC ( 36 ). Notch signaling pathway can inhibit or promote HCC cell apoptosis due to altered cellular and molecular environments ( 37 ). Notch signaling pathway regulates hepatocellular carcinoma cell apoptosis by “crosstalk” with other cell signaling pathways or directly affecting internal and external apoptosis pathways ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

Necroptosis-Related Genes Signatures Identified Molecular Subtypes and Underlying Mechanisms in Hepatocellular Carcinoma

Wei

Hou²,

et al. 2022

Front. Oncol.

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BackgroundAlthough emerging evidence supports the relationship between necroptosis (NEC) related genes and hepatocellular carcinoma (HCC), the contribution of these necroptosis-related genes to the development, prognosis, and immunotherapy of HCC is unclear.MethodsThe expression of genes and relevant clinical information were downloaded from TCGA-LIHC, LIRI-JP, GSE14520/NCI, GSE36376, GSE76427, GSE20140, GSE27150, and IMvigor210 datasets. Next, we used an unsupervised clustering method to assign the samples into phenotype clusters base on 15 necroptosis-related genes. Subsequently, we constructed a NEC score based on NEC phenotype-related prognostic genes to quantify the necroptosis related subtypes of individual patients.ResultsWe divided the samples into the high and low NEC score groups, and the high NEC score showed a poor prognosis. Simultaneously, NEC score is an effective and stable model and had a good performance in predicting the prognosis of HCC patients. A high NEC score was characterized by activation of the stroma and increased levels of immune infiltration. A high NEC score was also related to low expression of immune checkpoint molecules (PD-1/PD-L1). Importantly, the established NEC score would contribute to predicting the response to anti-PD-1/L1 immunotherapy.ConclusionsOur study provide a comprehensive analysis of necroptosis-related genes in HCC. Stratification based on the NEC score may enable HCC patients to benefit more from immunotherapy and help identify new cancer treatment strategies.

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Notch Signaling and Liver Cancer

Cited by 25 publications

References 76 publications

Membrane tension-mediated stiff and soft tumor subtypes closely associated with prognosis for prostate cancer patients

Membrane tension-mediated stiff and soft tumor subtypes closely associated with prognosis for prostate cancer patients

Roxadustat induces hepatotoxicity in zebrafish embryos via inhibiting Notch signaling

Necroptosis-Related Genes Signatures Identified Molecular Subtypes and Underlying Mechanisms in Hepatocellular Carcinoma

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