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inhibitors and stimulators of notch signaling in glioma

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https://www.readbyqxmd.com/read/22093097/notch1-promotes-glioma-cell-migration-and-invasion-by-stimulating-%C3%AE-catenin-and-nf-%C3%AE%C2%BAb-signaling-via-akt-activation
#1
Xiaohua Zhang, Tao Chen, Jiannan Zhang, Qin Mao, Shanquan Li, Wenhao Xiong, Yongming Qiu, Qiuling Xie, Jianwei Ge
The Notch signaling pathway has been implicated in both developmental processes and tumorigenesis. Aberrant Notch signaling has been repeatedly demonstrated to facilitate the proliferation and survival of glioma cells by regulating downstream effectors or other signaling pathways. In glioblastoma multiforme specimens from 59 patients, Notch1 was highly expressed in tumor tissues compared with normal brain tissues, and this expression was correlated with elevated AKT phosphorylation and Snail expression. Increased nuclear localization of β-catenin and p50 as well as enhanced IKKα/AKT interaction were also observed in glioma tissues...
February 2012: Cancer Science
https://www.readbyqxmd.com/read/18676808/inhibitor-of-differentiation-4-drives-brain-tumor-initiating-cell-genesis-through-cyclin-e-and-notch-signaling
#2
Hye-Min Jeon, Xun Jin, Joong-Seob Lee, Se-Yeong Oh, Young-Woo Sohn, Hyo-Jung Park, Kyeung Min Joo, Woong-Yang Park, Do-Hyun Nam, Ronald A DePinho, Lynda Chin, Hyunggee Kim
Cellular origins and genetic factors governing the genesis and maintenance of glioblastomas (GBM) are not well understood. Here, we report a pathogenetic role of the developmental regulator Id4 (inhibitor of differentiation 4) in GBM. In primary murine Ink4a/Arf(-/-) astrocytes, and human glioma cells, we provide evidence that enforced Id4 can drive malignant transformation by stimulating increased cyclin E to produce a hyperproliferative profile and by increased Jagged1 expression with Notch1 activation to drive astrocytes into a neural stem-like cell state...
August 1, 2008: Genes & Development
https://www.readbyqxmd.com/read/18636433/tgf-alpha-induces-upregulation-and-nuclear-translocation-of-hes1-in-glioma-cell
#3
Yingfeng Zheng, Ling Lin, Zhihong Zheng
Both the Notch-signaling pathway and extracellular signal regulated kinase (ERK) cascade are involved in a wide variety of biological processes, such as proliferation, differentiation, survival, and tumorigenesis. Their dysregulation in recent studies have been shown to be associated with glioma formation. Here, we show that transforming growth factor-alpha (TGF-alpha) stimulated glioma cell line U251 growth and can partly compensate for the inhibitory effect of Notch-signaling inhibitor DAPT. The effect of TGF-alpha on ERK1/2 phosphorylation was prompt and transient and could be inhibited by mitogen-activated/extracellular signal-regulated kinase kinase 1/2 (MEK1/2) specific inhibitor PD98059...
August 2008: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/18339870/regulation-of-cxcr4-by-the-notch-ligand-delta-like-4-in-endothelial-cells
#4
Cassin Kimmel Williams, Marta Segarra, Maria De La Luz Sierra, Richard C A Sainson, Giovanna Tosato, Adrian L Harris
Gene-targeting studies have shown that Delta-like 4 (Dll4) is required for normal embryonic vascular remodeling, but the mechanisms underlying Dll4 regulatory functions are not well defined. We generated primary human umbilical vascular endothelial cells that express Dll4 protein to study Dll4 function and previously showed that Dll4 down-regulates vascular endothelial growth factor (VEGF) receptor 2 and NRP1 expression and inhibits VEGF function. We now report that expression of Dll4 in endothelial cells inhibited attachment and migration to stromal-derived growth factor 1 (SDF1) chemokine...
March 15, 2008: Cancer Research
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