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https://www.readbyqxmd.com/read/28086833/delta-like-4-notch-signaling-promotes-apc-min-tumor-initiation-through-angiogenic-and-non-angiogenic-related-mechanisms
#1
Marina Badenes, Alexandre Trindade, Hugo Pissarra, Luís Lopes-da-Costa, António Duarte
BACKGROUND: Delta like 4 (Dll4)/Notch signaling is a key regulator of tumor angiogenesis. Additionally, the role of Dll4 has been studied on tumor stem cells. However, as these cells are implicated in tumor angiogenesis, it is conceivable that the effect of Dll4 on these cells may be a consequence of its angiogenic function. Our aim was to evaluate the expression and dissect the functions of Dll4 in the Apc (Min/+) model of colorectal cancer. METHODS: We evaluated the protein expression pattern of Dll4 and other Notch members in the Apc (Min/+) tumors relatively to the normal gut and compared endothelial-specific with ubiquitous Dll4 knockout mice on an Apc (Min/+) background...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28069038/motility-of-glioblastoma-cells-is-driven-by-netrin-1-induced-gain-of-stemness
#2
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/28062361/redox-signaling-in-the-gastrointestinal-tract
#3
REVIEW
Salvador Pérez, Raquel Taléns-Visconti, Sergio Rius-Pérez, Isabela Finamor, Juan Sastre
Redox signaling regulates physiological self-renewal, proliferation, migration and differentiation in gastrointestinal epithelium by modulating Wnt/β-catenin and Notch signaling pathways mainly through NADPH oxidases (NOXs). In the intestine, intracellular and extracellular thiol redox status modulates the proliferative potential of epithelial cells. Furthermore, commensal bacteria contribute to intestine epithelial homeostasis through NOX1- and dual oxidase 2-derived reactive oxygen species (ROS). The loss of redox homeostasis is involved in the pathogenesis and development of a wide diversity of gastrointestinal disorders, such as Barrett's esophagus, esophageal adenocarcinoma, peptic ulcer, gastric cancer, ischemic intestinal injury, celiac disease, inflammatory bowel disease and colorectal cancer...
January 3, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28061797/natural-compounds-targeting-major-cell-signaling-pathways-a-novel-paradigm-for-osteosarcoma-therapy
#4
REVIEW
Pablo Angulo, Gaurav Kaushik, Dharmalingam Subramaniam, Prasad Dandawate, Kathleen Neville, Katherine Chastain, Shrikant Anant
Osteosarcoma is the most common primary bone cancer affecting children and adolescents worldwide. Despite an incidence of three cases per million annually, it accounts for an inordinate amount of morbidity and mortality. While the use of chemotherapy (cisplatin, doxorubicin, and methotrexate) in the last century initially resulted in marginal improvement in survival over surgery alone, survival has not improved further in the past four decades. Patients with metastatic osteosarcoma have an especially poor prognosis, with only 30% overall survival...
January 7, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28061457/prognostic-roles-of-mrna-expression-of-notch-receptors-in-non-small-cell-lung-cancer
#5
Jianwen Xiong, Xiaoqiang Zhang, Xianglai Chen, Yiping Wei, De-Guo Lu, Yun-Wei Han, Jianjun Xu, Dongliang Yu
Notch signalling is aberrantly activated in human non-small cell lung cancer (NSCLC). Nevertheless, the prognostic roles of mRNA expression of four Notch receptors in NSCLC patients remain elusive. In this report, we reported the prognostic roles of Notch receptors in a total of 1,926 NSCLC patients through "The Kaplan-Meier plotter" (KM plotter) database which is capable to assess the effect of 22,277 genes on survival of NSCLC patients. We found that mRNA high expression level of Notch1 was associated with better overall survival (OS) for all NSCLC patients, hazard ratio (HR) 0...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28060745/expression-of-notch1-and-numb-in-small-cell-lung-cancer
#6
Hajime Kikuchi, Jun Sakakibara-Konishi, Megumi Furuta, Hiroshi Yokouchi, Hiroshi Nishihara, Shigeo Yamazaki, Hidetaka Uramoto, Fumihiro Tanaka, Masao Harada, Kenji Akie, Fumiko Sugaya, Yuka Fujita, Kei Takamura, Tetsuya Kojima, Toshiyuki Harada, Mitsunori Higuchi, Osamu Honjo, Yoshinori Minami, Naomi Watanabe, Satoshi Oizumi, Hiroyuki Suzuki, Takashi Ishida, Hirotoshi Dosaka-Akita, Hiroshi Isobe, Mitsuru Munakata, Masaharu Nishimura
Notch signaling in tumorigenesis functions as an oncogene or tumor suppressor according to the type of malignancy. Numb represses intracellular Notch signaling. Previous studies have demonstrated that Notch signaling suppresses the proliferation of small cell lung cancer (SCLC) cell lines. However, in SCLC, the association between Notch1 and Numb expression and clinicopathological factors or prognosis has remained unclear. In this study, we evaluated the expression of Notch1 and Numb in SCLC. We immunohistochemically assessed 125 SCLCs that were surgically resected at 16 institutions participating in either the Hokkaido Lung Cancer Clinical Study Group Trial (HOT) or the Fukushima Investigative Group for Healing Thoracic Malignancy (FIGHT) between 2003 and 2013...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28058624/zebrafish-phenotypic-screen-identifies-novel-notch-antagonists
#7
Vithya Velaithan, Kazuhide Shaun Okuda, Mei Fong Ng, Norazwana Samat, Sze Wei Leong, Siti Munirah Mohd Faudzi, Faridah Abas, Khozirah Shaari, Sok Ching Cheong, Pei Jean Tan, Vyomesh Patel
Zebrafish represents a powerful in vivo model for phenotype-based drug discovery to identify clinically relevant small molecules. By utilizing this model, we evaluated natural product derived compounds that could potentially modulate Notch signaling that is important in both zebrafish embryogenesis and pathogenic in human cancers. A total of 234 compounds were screened using zebrafish embryos and 3 were identified to be conferring phenotypic alterations similar to embryos treated with known Notch inhibitors...
January 5, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28050146/personalized-oncogenomics-in-the-management-of-gastrointestinal-carcinomas-early-experiences-from-a-pilot-study
#8
B S Sheffield, B Tessier-Cloutier, H Li-Chang, Y Shen, E Pleasance, K Kasaian, Y Li, S J M Jones, H J Lim, D J Renouf, D G Huntsman, S Yip, J Laskin, M Marra, D F Schaeffer
BACKGROUND: Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. METHODS: We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma...
December 2016: Current Oncology
https://www.readbyqxmd.com/read/28042023/diverse-pathways-of-epithelial-mesenchymal-transition-related-with-cancer-progression-and-metastasis-and-potential-effects-of-endocrine-disrupting-chemicals-on-epithelial-mesenchymal-transition-process
#9
Hae-Miru Lee, Kyung-A Hwang, Kyung-Chul Choi
Endocrine disrupting chemicals (EDCs) are natural or synthetic compounds that interfere with normal functions of natural hormones in the body, leading to a disruption of the endocrine system. Specifically, EDCs have the potential to cause formation of several hormone-dependent cancers, including breast, ovarian, and prostate cancers. Epithelial mesenchymal transition (EMT) process by which epithelial cells lose their cell polarity and cell-cell adhesion and acquire mesenchymal phenotype is closely associated with malignant transformation and the initiation of cancer metastasis...
December 29, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28036048/targeting-notch3-in-hepatocellular-carcinoma-molecular-mechanisms-and-therapeutic-perspectives
#10
REVIEW
Catia Giovannini, Luigi Bolondi, Laura Gramantieri
The Notch signaling pathway is a very conserved system that controls embryonic cell fate decisions and the maintenance of adult stem cells through cell to cell communication. Accumulating evidence support the relevance of Notch signaling in different human diseases and it is one of the most commonly activated signaling pathways in cancer. This review focuses mainly on the role of Notch3 signaling in hepatocellular carcinoma and its potential therapeutic applications against this malignancy. In this regard, the crosstalk between Notch and p53 may play an important role...
December 28, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28035075/the-hippo-signaling-pathway-provides-novel-anti-cancer-drug-targets
#11
REVIEW
June Sung Bae, Sun Mi Kim, Ho Lee
The Hippo signaling pathway plays a crucial role in cell proliferation, apoptosis, differentiation, and development. Major effectors of the Hippo signaling pathway include the transcriptional co-activators Yes-associated protein 1 (YAP) and WW domain-containing transcription regulator protein 1 (TAZ). The transcriptional activities of YAP and TAZ are affected by interactions with proteins from many diverse signaling pathways as well as responses to the external environment. High YAP and TAZ activity has been observed in many cancer types, and functional dysregulation of Hippo signaling enhances the oncogenic properties of YAP and TAZ and promotes cancer development...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28018099/understanding-the-role-of-pin1-in-hepatocellular-carcinoma
#12
REVIEW
Chi-Wai Cheng, Ka-Wai Leong, Eric Tse
PIN1 is a peptidyl-prolyl cis/trans isomerase that binds and catalyses isomerization of the specific motif comprising a phosphorylated serine or threonine residue preceding a proline (pSer/Thr-Pro) in proteins. PIN1 can therefore induce conformational and functional changes of its interacting proteins that are regulated by proline-directed serine/threonine phosphorylation. Through this phosphorylation-dependent prolyl isomerization, PIN1 fine-tunes the functions of key phosphoproteins (e.g., cyclin D1, survivin, β-catenin and x-protein of hepatitis B virus) that are involved in the regulation of cell cycle progression, apoptosis, proliferation and oncogenic transformation...
December 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28012856/increased-fndc5-irisin-expression-in-human-hepatocellular-carcinoma
#13
Melania Gaggini, Manuela Cabiati, Serena Del Turco, Teresa Navarra, Paolo De Simone, Franco Filipponi, Silvia Del Ry, Amalia Gastaldelli, Giuseppina Basta
The fibronectin type III domain containing 5 (FNDC5)/Irisin, a novel energy-regulating hormone, is associated with lipid and carbohydrate metabolism. It is produced in low amounts by normal hepatic tissue, while in human hepatocellular carcinoma (HCC), in which aberrant de novo lipogenesis (DNL) occurs, the hepatic expression of FNDC5/Irisin is still unknown. The gene expression of FNDC5/Irisin, associated to key regulators of DNL, inflammation and cancer progression was evaluated in liver tissue of 18 patients with HCC undergoing liver transplantation and of 18 deceased donors...
December 21, 2016: Peptides
https://www.readbyqxmd.com/read/28007595/the-notch-ligand-delta-like-3-promotes-tumor-growth-and-inhibits-notch-signaling-in-lung-cancer-cells-in-mice
#14
San-Ming Deng, Xian-Chun Yan, Liang Liang, Li Wang, Yuan Liu, Juan-Li Duan, Zi-Yan Yang, Tian-Fang Chang, Bai Ruan, Qi-Jun Zheng, Hua Han
Although it has been suggested that Dll3, one of the Notch ligands, promotes the proliferation and inhibits the apoptosis of cancer cells, the role of Dll3 in cancers remains unclear. In this study, we found that in the murine Lewis lung carcinoma (LLC) cells, the level of Dll3 mRNA changed upon tumor microenvironment (TME) stimulation, namely, decreased under hypoxia or stimulated with tumor necrosis factor (TNF)-α. Dll3 was also expressed at higher level in human lung carcinoma tissues than in the para-carcinoma tissues...
December 19, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28007318/suberoylanilide-hydroxamic-acid-a-histone-deacetylase-inhibitor-alters-multiple-signaling-pathways-in-hepatocellular-carcinoma-cell-lines
#15
Selvi Kunnimalaiyaan, Kevin Sokolowski, T Clark Gamblin, Muthusamy Kunnimalaiyaan
INTRODUCTION: Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, has preclinical efficacy in hepatocellular carcinoma (HCC), despite an unclear molecular mechanism. We sought to further investigate the effects of SAHA on HCC. We hypothesize SAHA will inhibit HCC cellular proliferation through apoptosis and aid in further profiling SAHA's effect on HCC oncogenic pathways. METHODS: HCC cell lines were treated with various concentrations of SAHA...
December 11, 2016: American Journal of Surgery
https://www.readbyqxmd.com/read/27999207/roles-of-gsk-3-and-micrornas-on-epithelial-mesenchymal-transition-and-cancer-stem-cells
#16
REVIEW
James A McCubrey, Timothy L Fitzgerald, Li V Yang, Kvin Lertpiriyapong, Linda S Steelman, Stephen L Abrams, Giuseppe Montalto, Melchiorre Cervello, Luca M Neri, Lucio Cocco, Alberto M Martelli, Piotr Laidler, Joanna DuliÅ Ska-Litewka, Dariusz Rakus, Agnieszka Gizak, Ferdinando Nicoletti, Luca Falzone, Saverio Candido, Massimo Libra
Various signaling pathways exert critical roles in the epithelial to mesenchymal transition (EMT) and cancer stem cells (CSCs). The Wnt/beta-catenin, PI3K/PTEN/Akt/mTORC, Ras/Raf/MEK/ERK, hedgehog (Hh), Notch and TP53 pathways elicit essential regulatory influences on cancer initiation, EMT and progression. A common kinase involved in all these pathways is moon-lighting kinase glycogen synthase kinase-3 (GSK-3). These pathways are also regulated by micro-RNAs (miRs). TP53 and components of these pathways can regulate the expression of miRs...
December 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27999190/leptin-notch-signaling-axis-is-involved-in-pancreatic-cancer-progression
#17
Adriana Harbuzariu, Antonio Rampoldi, Danielle S Daley-Brown, Pierre Candelaria, Tia L Harmon, Crystal C Lipsey, Derrick J Beech, Alexander Quarshie, Gabriela Oprea Ilies, Ruben R Gonzalez-Perez
Pancreatic cancer (PC) shows a high death rate. PC incidence and prognosis are affected by obesity, a pandemic characterized by high levels of leptin. Notch is upregulated by leptin in breast cancer. Thus, leptin and Notch crosstalk could influence PC progression. Here we investigated in PC cell lines (BxPC-3, MiaPaCa-2, Panc-1, AsPC-1), derived tumorspheres and xenografts whether a functional leptin-Notch axis affects PC progression and expansion of pancreatic cancer stem cells (PCSC). PC cells and tumorspheres were treated with leptin and inhibitors of Notch (gamma-secretase inhibitor, DAPT) and leptin (iron oxide nanoparticle-leptin peptide receptor antagonist 2, IONP-LPrA2)...
December 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27989769/adaptive-chromatin-remodeling-drives-glioblastoma-stem-cell-plasticity-and-drug-tolerance
#18
Brian B Liau, Cem Sievers, Laura K Donohue, Shawn M Gillespie, William A Flavahan, Tyler E Miller, Andrew S Venteicher, Christine H Hebert, Christopher D Carey, Scott J Rodig, Sarah J Shareef, Fadi J Najm, Peter van Galen, Hiroaki Wakimoto, Daniel P Cahill, Jeremy N Rich, Jon C Aster, Mario L Suvà, Anoop P Patel, Bradley E Bernstein
Glioblastoma, the most common and aggressive malignant brain tumor, is propagated by stem-like cancer cells refractory to existing therapies. Understanding the molecular mechanisms that control glioblastoma stem cell (GSC) proliferation and drug resistance may reveal opportunities for therapeutic interventions. Here we show that GSCs can reversibly transition to a slow-cycling, persistent state in response to targeted kinase inhibitors. In this state, GSCs upregulate primitive developmental programs and are dependent upon Notch signaling...
December 2, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27983919/overexpression-of-per3-inhibits-self-renewal-capability-and-chemoresistance-of-colorectal-cancer-stem-like-cells-via-inhibition-of-notch-and-%C3%AE-catenin-signaling
#19
Feng Zhang, Hong Sun, Sai Zhang, Xin Yang, Guogang Zhang, Tao Su
PER3, a circadian clock gene, plays an important role in colorectal cancer, but its action and underlying mechanisms incolorectal cancer stem-like cells (CSCs) remain unclear. Here, the colorectal CSCs were enriched in colorectal HCT-116 sphere-forming cells, expressing lower levels of stem cell markers CD133, CD44, LGR5, Sox2 compared with HCT-116 cells. And drug-resistant strain from HCT-116 was established. Western blot and qRT-PCR analysis showed that PER3 was downregulated in colorectal CSCs and drug-resistant HCT-116...
October 26, 2016: Oncology Research
https://www.readbyqxmd.com/read/27974417/notch-inhibitor-shows-modest-efficacy
#20
(no author information available yet)
Data from a phase I study indicate that LY3039478 is modestly effective against a range of advanced or metastatic cancers. The investigational Notch-signaling inhibitor induced partial responses and stable disease in patients with breast cancer and rare malignancies such as adenoid cystic carcinoma and leiomyosarcoma.
December 14, 2016: Cancer Discovery
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