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notch signaling in glioma

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https://www.readbyqxmd.com/read/29290950/human-fibulin-3-protein-variant-expresses-anti-cancer-effects-in-the-malignant-glioma-extracellular-compartment-in-intracranial-xenograft-models
#1
Yanyan Li, Yuan Hu, Chuanjin Liu, Qingyue Wang, Xiaoxiao Han, Yong Han, Xue-Shun Xie, Xiong-Hui Chen, Xiang Li, Eric R Siegel, Kambiz Afrasiabi, Mark E Linskey, You-Xin Zhou, Yi-Hong Zhou
Background: Decades of cytotoxic and more recently immunotherapy treatments for malignant glioma have had limited success due to dynamic intra-tumoral heterogeneity. The dynamic interplay of cancer cell subpopulations has been found to be under the control of proteins in the cancer microenvironment. EGF-containing fibulin-like extracellular matrix protein (EFEMP1) (also fibulin-3) has the multiple functions of suppressing cancer growth and angiogenesis, while promoting cancer cell invasion...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29251609/-the-role-of-micro-rna-in-the-regulation-of-signal-pathways-in-gliomas
#2
REVIEW
O I Kit, D I Vodolazhsky, E E Rostorguev, D H Porksheyan, S B Panina
Gliomas are invasive brain tumors with high rates of recurrence and mortality. Glioblastoma multiforme (GBM) is the most deadly form of glioma with nearly 100% rate of recurrence and unfavorable prognosis in patients. Micro-RNAs (miR) are the class of wide-spread short non-coding RNAs that inhibit translation via binding to the mRNA of target genes. The aim of the present review is to analyze recent studies and experimental results concerning aberrant expression profiles of miR, which target components of the signaling pathways Hedgehog, Notch, Wnt, EGFR, TGFb, HIF1a in glioma/glioblastoma...
November 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/29251326/isoliquiritigenin-inhibits-the-proliferation-and-induces-the-differentiation-of-human-glioma-stem-cells
#3
Yuliang Lin, Hongjun Sun, Ying Dang, Zhiyun Li
Glioma stem cells (GSCs) have been proven to be resistant to various therapeutic strategies, such as temozolomide chemotherapy and radiotherapy, leading to glioma recurrence. Isoliquiritigenin (ISL), a menber of the flavonoids isolated from liquorice has been found to be a potent stimulator of cell differentiation and has potential application for treating various types of cancer including human brain glioma. However, the antitumor activity of ISL on GSCs and the signaling pathway underlying its therapeutic effects are poorly understood...
February 2018: Oncology Reports
https://www.readbyqxmd.com/read/29198941/hypoxic-induction-of-vasorin-regulates-notch1-turnover-to-maintain-glioma-stem-like-cells
#4
Jianghong Man, Xingjiang Yu, Haidong Huang, Wenchao Zhou, Chaomei Xiang, Haohao Huang, Lucio Miele, Zhenggang Liu, Gurkan Bebek, Shideng Bao, Jennifer S Yu
Tumor hypoxia is associated with poor patient survival and is a characteristic of glioblastoma. Notch signaling is implicated in maintaining glioma stem-like cells (GSCs) within the hypoxic niche, although the molecular mechanisms linking hypoxia to Notch activation have not been clearly delineated. Here we show that Vasorin is a critical link between hypoxia and Notch signaling in GSCs. Vasorin is preferentially induced in GSCs by a HIF1α/STAT3 co-activator complex and stabilizes Notch1 protein at the cell membrane...
November 23, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29196129/stanniocalcin-1-augments-stem-like-traits-of-glioblastoma-cells-through-binding-and-activating-notch1
#5
Yong Li, Zhi-Cheng He, Xiao-Ning Zhang, Qing Liu, Cong Chen, Zheng Zhu, Qian Chen, Yu Shi, Xiao-Hong Yao, You-Hong Cui, Xia Zhang, Yan Wang, Hsiang-Fu Kung, Yi-Fang Ping, Xiu-Wu Bian
Glioblastoma (GBM) is a fatal tumor and comprises heterogeneous cells in which a subpopulation with stem cell-like properties is included. Cancer cells with stem cell-like properties account for tumor initiation, drug resistance and recurrence. To identify and characterize specific factors in regulating stem-like traits is critical for GBM therapeutic. Here, we showed that Stanniocalcin-1 (STC1), a secretory glycoprotein, functions as a novel stimulator for stem-like traits of GBM cells. We found STC1 was prominently expressed in glioma spheres which are mainly comprised of glioma stem-like cells...
November 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29146721/development-of-a-function-blocking-antibody-against-fibulin-3-as-targeted-reagent-for-glioblastoma
#6
Mohan Sobhana Nandhu, Prajna Behera, Vivek Bhaskaran, Sharon L Longo, Lina M Barrera-Arenas, Sadhak Sengupta, Diego J Rodriguez-Gil, E Antonio Chiocca, Mariano S Viapiano
PURPOSE: We sought a novel approach against glioblastomas (GBM) focused on targeting signaling molecules localized in the tumor extracellular matrix (ECM). We investigated fibulin-3, a glycoprotein that forms the ECM scaffold of GBMs and promotes tumor progression by driving Notch and NF-kB signaling. EXPERIMENTAL DESIGN: We used deletion constructs to identify a key signaling motif of fibulin-3. A monoclonal antibody (mAb428.2) was generated against this epitope and extensively validated for specific detection of human fibulin-3...
November 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28977881/microrna-145-induces-apoptosis-of-glioma-cells-by-targeting-bnip3-and-notch-signaling
#7
Yan Du, Juan Li, Tao Xu, Dan-Dan Zhou, Lei Zhang, Xiao Wang
MicroRNAs (miRNAs) are involved in the pathogenesis of various human cancers. Here we show that miR-145 expression is decreased in human glioma samples, rat glioma tissues, and glioma cell lines, while expression of BNIP3 is increased. Over-expression of miR-145 or suppression of BNIP3 induced glioma cell apoptosis. BNIP3 is localized in the nucleus in glioma cells, and miR-145 inhibits BNIP3 expression by binding to the 3' untranslated region of its mRNA. Interestingly, miR-145 and BNIP3 regulate glioma cell apoptosis by modulating Notch signaling...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28950865/glioma-cell-fate-decisions-mediated-by-dll1-jag1-fringe-in-notch1-signaling-pathway
#8
Xiaofei Shi, Ruiqi Wang
BACKGROUND: The Notch family of proteins plays a vital role in determining cell fates, such as proliferation, differentiation, and apoptosis. It has been shown that Notch1 and its ligands, Dll1 and Jag1, are overexpressed in many glioma cell lines and primary human gliomas. The roles of Notch1 in some cancers have been firmly established, and recent data implicate that it plays important roles in glioma cell fate decisions. This paper focuses on devising a specific theoretical framework that incorporates Dll1, Jag1, and Fringe in Notch1 signaling pathway to explore their functional roles of these proteins in glioma cells in the tumorigenesis and progression of human gliomas, and to study how glioma cell fate decisions are modulated by both trans-activation and cis-inhibition...
September 21, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28800786/knockdown-of-long-noncoding-rna-linc0000125-suppresses-cellular-proliferation-and-invasion-in-glioma-cells-by-regulating-mir-4775
#9
Zhankun Zhu, Jinhua Dai, Yufeng Liao, Jianbo Ma, Wei Zhou
Long noncoding RNAs (lncRNAs) play an important role in various biological properties of glioma cells. Herein, we aimedto elucidate the function and the possible molecular mechanisms of long intergenic non-coding RNA 152 (LINC00152) in glioma cells. Relative expressions of LINC00152, miR-4775 and CDK6 in U-118 MG cells were regulated by transfections. Thereafter, cell viability, migration, invasion and apoptosis were analyzed by CCK8, Transwell and flow cytometry assays. Dual-luciferase reporter assay was conducted to validate the target genes of LINC00152 and miR-4775...
August 11, 2017: Oncology Research
https://www.readbyqxmd.com/read/28658662/microrna-145-induces-apoptosis-of-glioma-cells-by-targeting-bnip3-and-notch-signaling
#10
Yan Du, Juan Li, Tao Xu, Dan-Dan Zhou, Lei Zhang, Xiao Wang
MicroRNAs (miRNAs) are involved in the pathogenesis of various human cancers. Here we show that miR-145 expression is decreased in human glioma samples, rat glioma tissues, and glioma cell lines, while expression of BNIP3 is increased. Over-expression of miR-145 or suppression of BNIP3 induced glioma cell apoptosis. BNIP3 is localized in the nucleus in glioma cells, and miR-145 inhibits BNIP3 expression by binding to the 3' untranslated region of its mRNA. Interestingly, miR-145 and BNIP3 regulate glioma cell apoptosis by modulating Notch signaling...
June 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28571041/cbf1-is-clinically-prognostic-and-serves-as-a-target-to-block-cellular-invasion-and-chemoresistance-of-emt-like-glioblastoma-cells
#11
D Maciaczyk, D Picard, L Zhao, K Koch, D Herrera-Rios, G Li, V Marquardt, D Pauck, T Hoerbelt, W Zhang, D M Ouwens, M Remke, T Jiang, H J Steiger, J Maciaczyk, U D Kahlert
BACKGROUND: Glioblastoma is the most common and most lethal primary brain cancer. CBF1 (also known as Recombination signal Binding Protein for immunoglobulin kappa J, RBPJ) is the cardinal transcriptional regulator of the Notch signalling network and has been shown to promote cancer stem-like cells (CSCs) in glioblastoma. Recent studies suggest that some of the malignant properties of CSCs are mediated through the activation of pro-invasive programme of epithelial-to-mesenchymal transition (EMT)...
June 27, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28416488/activation-of-notch-signaling-by-tenascin-c-promotes-growth-of-human-brain-tumor-initiating-cells
#12
Susobhan Sarkar, Reza Mirzaei, Franz J Zemp, Wu Wei, Donna L Senger, Stephen M Robbins, V Wee Yong
Oncogenic signaling by NOTCH is elevated in brain tumor-initiating cells (BTIC) in malignant glioma, but the mechanism of its activation is unknown. Here we provide evidence that tenascin-C (TNC), an extracellular matrix protein prominent in malignant glioma, increases NOTCH activity in BTIC to promote their growth. We demonstrate the proximal localization of TNC and BTIC in human glioblastoma specimens and in orthotopic murine xenografts of human BTIC implanted intracranially. In tissue culture, TNC was superior amongst several extracellular matrix proteins in enhancing the sphere-forming capacity of glioma patient-derived BTIC...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28380416/actin-cytoskeleton-regulator-arp2-3-complex-is-required-for-dll1-activating-notch1-signaling-to-maintain-the-stem-cell-phenotype-of-glioma-initiating-cells
#13
Chen Zhang, Long Hai, Meng Zhu, Shengping Yu, Tao Li, Yu Lin, Bo Liu, Xingchen Zhou, Lei Chen, Pengfei Zhao, Hua Zhou, Yubao Huang, Kai Zhang, Bingcheng Ren, Xuejun Yang
Glioblastoma (GBM) is the most common and lethal primary intracranial tumor. Actin cytoskeleton regulator Arp2/3 complex stimulates glioma cell motility and migration, and thus triggers tumor invasion. However, little is known regarding the role of actin cytoskeleton in maintaining the stem cell phenotype. Here, we showed that Arp2/3 complex improved stem cell phenotype maintenance through sustaining the activated Notch signaling. ShRNA targeting Notch ligand Delta-like 1 (DLL1) decreased CD133 and Nestin expression, and impaired the self-renewal ability of CD133+ U87-MG and U251-MG glioma cells, indicating DLL1/Notch1 signaling promoted stem cell phenotype maintenance...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28325280/mir-134-a-human-cancer-suppressor
#14
REVIEW
Jing-Yu Pan, Feng Zhang, Cheng-Cao Sun, Shu-Jun Li, Guang Li, Feng-Yun Gong, Tao Bo, Jing He, Rui-Xi Hua, Wei-Dong Hu, Zhan-Peng Yuan, Xin Wang, Qi-Qiang He, De-Jia Li
MicroRNAs (miRNAs) are small noncoding RNAs approximately 20-25 nt in length, which play crucial roles through directly binding to corresponding 3' UTR of targeted mRNAs. It has been reported that miRNAs are involved in numerous of diseases, including cancers. Recently, miR-134 has been identified to dysregulate in handles of human cancers, such as lung cancer, glioma, breast cancer, colorectal cancer, and so on. Increasing evidence indicates that miR-134 is essential for human carcinoma and participates in tumor cell proliferation, apoptosis, invasion and metastasis, drug resistance, as well as cancer diagnosis, treatment, and prognosis...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28259943/sclareolide-enhances-gemcitabine%C3%A2-induced-cell-death-through-mediating-the-nicd-and-gli1-pathways-in-gemcitabine%C3%A2-resistant-human-pancreatic-cancer
#15
Sheng Chen, Ye Wang, Wen-Long Zhang, Mao-Sheng Dong, Jian-Hua Zhang
Pancreatic cancer is a type of cancer, which rapidly develops resistance to chemotherapy. Gemcitabine is the treatment used clinically, however, gemcitabine resistance leads to limited efficacy and patient survival rates of only a few months following diagnosis. The aim of the present study was to investigate the mechanisms underlying gemcitabine resistance in pancreatic cancer and to select targeted agents combined with gemcitabine to promote the treatment of pancreatic cancer. Panc‑1 and ASPC‑1 human pancreatic cancer cells (HPCCs) were used to establish the experimental model, and HPCCs were exposed to gemcitabine of serially increased concentrations to generate gemcitabine‑resistant cells (GR‑HPCCs)...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28255276/melatonin-inhibits-glioblastoma-stem-like-cells-through-suppression-of-ezh2-notch1-signaling-axis
#16
Xiangrong Zheng, Bo Pang, Guangyan Gu, Taihong Gao, Rui Zhang, Qi Pang, Qian Liu
Glioblastoma stem-like cells (GSCs) play essential roles in glioma growth, radio- and chemo-resistance, and recurrence. Elimination of GSCs has therefore become a key strategy and challenge in glioblastoma therapy. Here, we show that melatonin, an indolamine derived from I-tryptophan, significantly inhibited viability and self-renewal ability of GSCs accompanied by a decrease of stem cell markers. We have identified EZH2-NOTCH1 signaling as the key signal pathway that regulated the effects of melatonin in the GSCs...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28216164/conversion-of-glioma-cells-to-glioma-stem-like-cells-by-angiocrine-factors
#17
Jun-Kyum Kim, Hye-Min Jeon, Hee-Young Jeon, Se-Yeong Oh, Eun-Jung Kim, Xiong Jin, Se-Hoon Kim, Sung-Hak Kim, Xun Jin, Hyunggee Kim
Glioma stem-like cells (GSCs) contribute to tumor initiation, progression, and therapeutic resistance, but their cellular origin remains largely unknown. Here, using a stem/progenitor cell-fate tracking reporter system in which eGFP is expressed by promoter of OCT4 that is activated in stem/progenitor cells, we demonstrate that eGFP-negative glioma cells (GCs) became eGFP-positive-GCs in both in vitro cultures and in vivo xenografts. These eGFP-positive-GCs exhibited GSC features and primarily localized to the perivascular region in tumor xenografts, similar to the existence of OCT4-expressing GCs in the perivascular region of human glioblastoma specimens...
February 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28081466/long-non-coding-rna-zfas1-is-an-unfavourable-prognostic-factor-and-promotes-glioma-cell-progression-by-activation-of-the-notch-signaling-pathway
#18
Kai Gao, Zhiwu Ji, Kun She, Qingyan Yang, Lianbin Shao
Survival of patients with glioma remains poor, which is largely attributed to active carcinogenesis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play key roles in tumor initiation and progression. However, the function of lncRNA ZFAS1 in glioma is still unclear. In the current study, we found that ZFAS1 was upregulated in glioma tissues and cell lines. High ZFAS1 expression in glioma tissues was significantly correlated with advanced tumor stage and poor overall survival. Furthermore, in vitro assays demonstrated that ZFAS1 inhibition significantly suppressed glioma cell proliferation, migration and invasion...
March 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28069038/motility-of-glioblastoma-cells-is-driven-by-netrin-1-induced-gain-of-stemness
#19
Irene Ylivinkka, Harri Sihto, Olli Tynninen, Yizhou Hu, Aki Laakso, Riku Kivisaari, Pirjo Laakkonen, Jorma Keski-Oja, Marko Hyytiäinen
BACKGROUND: Glioblastoma is an untreatable brain cancer. The tumors contain a population of stem-like cells which are highly invasive and resistant to therapies. These cells are the main reason for the lethality of glioblastoma. Extracellular guidance molecule netrin-1 promotes the invasiveness and survival of various cancer cell types. We have previously found that netrin-1 activates Notch signaling, and Notch signaling associates with cell stemness. Therefore, we have here investigated the effects of netrin-1 on glioblastoma pathogenesis and glioblastoma cell stemness...
January 9, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28060761/identification-of-micrornas-associated-with-glioma-diagnosis-and-prognosis
#20
Xinyun Ye, Wenjin Wei, Zhengyu Zhang, Chunming He, Ruijin Yang, Jinshi Zhang, Zhiwu Wu, Qianliang Huang, Qiuhua Jiang
The sensitivity and specificity of microRNAs (miRNAs) for diagnosing glioma are controversial. We therefore performed a meta-analysis to systematically identify glioma-associated miRNAs. We initially screened five miRNA microarray datasets to evaluate the differential expression of miRNAs between glioma and normal tissues. We next compared the expression of the miRNAs in different organs and tissues to assess the sensitivity and specificity of the differentially expressed miRNAs in the diagnosis of glioma. Finally, pathway analysis was performed using GeneGO...
April 18, 2017: Oncotarget
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