Browsing by Subject "Notch signaling"

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    Notch signaling in prostate cancer: refining a therapeutic opportunity
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Su, Qingtai; Xin, Li
    y. Notch is an evolutionarily conserved signaling pathway that plays a critical role in specifying cell fate and regulating tissue homeostasis and carcinogenesis. Studies using organ cultures and genetically engineered mouse models have demonstrated that Notch signaling regulates prostate development and homeostasis. However, the role of the Notch signaling pathway in prostate cancer remains inconclusive. Many published studies have documented consistent deregulation of major Notch signaling components in human prostate cancer cell lines, mouse models for prostate cancers, and human prostate cancer specimens at both the mRNA and the protein levels. However, functional studies in human cancer cells by modulation of Notch pathway elements suggest both tumor suppressive and oncogenic roles of Notch. These controversies may originate from our inadequate understanding of the regulation of Notch signaling under versatile genetic contexts, and reflect the multifaceted and pleiotropic roles of Notch in regulating different aspects of prostate cancer cell biology, such as proliferation, metastasis, and chemo-resistance. Future comprehensive studies using various mouse models for prostate cancer may help clarify the role of Notch signaling in prostate cancer and provide a solid basis for determining whether and how Notch should be employed as a therapeutic target for prostate cancer.
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    Notch1 in oral squamous cell carcinoma
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Yoshida, Ryoji; Ito, Takaaki; Abdo Hassan, Wael; Nakayama, Hideki
    Notch signaling has been reported to be involved in several types of malignant tumors. However, the role and activation mechanisms of Notch signaling in oral squamous cell carcinoma (OSCC) remain poorly characterized. The present review focuses on the dual role of Notch signaling in OSCC. A number of expression and functional analyses demonstrated that Notch1 plays a crucial role in development and progression of OSCC. On the other hand, a tumor suppressive role of Notch1 was also suggested from studies, based on deep sequencing of cancer genomes. Interestingly, although some Notch1 mutations overlap in tumors from Caucasian and Asian patients, the overall spectrum of such mutations is vastly different between these cohorts. Accumulating evidence suggests that variation of Notch1 mutation signature may determine the role of Notch signaling in OSCC. As Notch is thought to act as an oncogene in a subset of OSCC, but also has a tumor suppression role, the role of Notch in OSCC seems to be highly context dependent.
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    Resveratrol can prevent CCl4-induced liver injury by inhibiting Notch signaling pathway
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Tanriverdi, Gamze; Kaya-Dagistanli, Fatma; Ayla, Sule; Demirci, Sibel; Eser, Mediha; Unal, Seda; Cengiz, Mujgan; Oktar, Huseyin
    We investigated whether Notch signaling was increased in an experimental liver fibrosis model and examined the effects of resveratrol on Notch expression. Rats were divided into four groups: the control group, injected with physiological saline; the CCl 4 group; the CCl 4 plus resveratrol group; and the resveratrol group. After treatment, immunostaining was performed to detect Notch1, Notch3, Notch4, transforming growth factor (TGF)-beta, alpha-smooth muscle actin (SMA), glial fibrillary acidic protein (GFAP), and proliferating cell nuclear antigen (PCNA), and TUNEL assays were performed to evaluate apoptosis. Sirius red staining was used to detect fibrosis. Samples were also biochemically evaluated for glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), lipid peroxidation, and protein oxidation. GSH, GPx, and catalase activities were significantly decreased (p<0.001) in the CCl 4 group. Distinct collagen accumulation was detected around the central vein and portal areas, and numbers of Notch1-, Notch3-, and Notch4-positive cells were significantly increased (p<0.001) in fibrotic areas in the CCl 4 group. Increased expression of Notch proteins in fibrotic areas may support the role of Notch in mediating signaling associated with liver fibrosis through activation of hepatic stellate and progenitor cells. In contrast, resveratrol prevented liver fibrosis by decreasing lipid peroxidation and may be effective for inhibiting Notch signaling.