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NEDD9

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https://www.readbyqxmd.com/read/28446718/baicalein-inhibits-pancreatic-cancer-cell-proliferation-and-invasion-via-suppression-of-nedd9-expression-and-its-downstream-akt-and-erk-signaling-pathways
#1
Rong-Tao Zhou, Mei He, Ze Yu, Yang Liang, Yuzhe Nie, Sheng Tai, Chun-Bo Teng
Baicalein, a flavone ingredient of Scutellaria baicalensis Georgi, is a promising anti-cancer agent. However, its potential anti-pancreatic cancer effects and the underlying mechanisms are still unclear. In this study, we showed that Baicalein not only induced apoptosis, but also suppressed proliferation, migration and invasion of two pancreatic cancer cell lines BxPC-3 and PANC-1 in a dose- and time-dependent manner. Notably, Baicalein exhibited low toxicity to normal human liver or kidney cells. We further discovered that Baicalein suppressed BxPC-3 and PANC-1 cell proliferation and invasion through targeting the expression of NEDD9, a Cas scaffolding protein, to decrease Akt and ERK activities...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28332553/mir-18a-counteracts-akt-and-erk-activation-to-inhibit-the-proliferation-of-pancreatic-progenitor-cells
#2
Xuyan Li, Zhenwu Zhang, Yunchao Li, Yicheng Zhao, Wenjun Zhai, Lin Yang, Delin Kong, Chunyan Wu, Zhenbao Chen, Chun-Bo Teng
Activation of endogenous stem/progenitor cells to repair injured tissues is an ideal option for disease treatment. However, adult pancreatic progenitor cells remain in a quiescent state in vivo. Thus, it is difficult to stimulate proliferation and differentiation in these progenitor cells, and the cause remains elusive. miR-17-92 cluster miRNAs are highly conserved in mammals and are expressed in multiple tissue stem/progenitor cells, but their role in pancreatic progenitor cells are less well known. In the present study, we demonstrate that miR-18a, but not the other members of the miR-17-92 gene cluster, inhibits the proliferation of pancreatic progenitor cells in vitro and ex vivo...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28273108/structure-based-mutational-analysis-of-icat-residues-mediating-negative-regulation-of-%C3%AE-catenin-co-transcriptional-activity
#3
Mélanie J Domingues, Juan Martinez-Sanz, Laura Papon, Lionel Larue, Liliane Mouawad, Jacky Bonaventure
ICAT (Inhibitor of β-CAtenin and TCF) is a small acidic protein that negatively regulates β-catenin co-transcriptional activity by competing with TCF/LEF factors in their binding to β-catenin superhelical core. In melanoma cells, ICAT competes with LEF1 to negatively regulate the M-MITF and NEDD9 target genes. The structure of ICAT consists of two domains: the 3-helix bundle N-terminal domain binds to β-catenin Armadillo (Arm) repeats 10-12 and the C-terminal tail binds to Arm repeats 5-9. To elucidate the structural mechanisms governing ICAT/β-catenin interactions in melanoma cells, three ICAT residues Y15, K19 and V22 in the N-terminal domain, contacting hydrophobic β-catenin residue F660, were mutated and interaction was assessed by immunoprecipitation...
2017: PloS One
https://www.readbyqxmd.com/read/28235899/dual-targeting-of-mesenchymal-and-amoeboid-motility-hinders-metastatic-behavior
#4
Brandon C Jones, Laura C Kelley, Yuriy V Loskutov, Kristina M Marinak, Varvara K Kozyreva, Matthew B Smolkin, Elena N Pugacheva
Commonly upregulated in human cancers, the scaffolding protein NEDD9/HEF1 is a known regulator of mesenchymal migration and cancer cell plasticity. However, the functional role of NEDD9 as a regulator of different migration/invasion modes in the context of breast cancer metastasis is currently unknown. Here, it is reported that NEDD9 is necessary for both mesenchymal and amoeboid individual cell migration/invasion in triple-negative breast cancer (TNBC). NEDD9 deficiency results in acquisition of the amoeboid morphology, but severely limits all types of cell motility...
February 24, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28223315/the-focal-adhesion-targeting-domain-of-p130cas-confers-a-mechanosensing-function
#5
Peta M Bradbury, Kylie Turner, Camilla Mitchell, Kaitlyn R Griffin, Shiloh Middlemiss, Loretta Lau, Rebecca Dagg, Elena Taran, Justin Cooper-White, Ben Fabry, Geraldine M O'Neill
Members of the Cas family of focal adhesion proteins contain a highly conserved C-terminal focal adhesion targeting (FAT) domain. To determine the role of the FAT domain in these proteins, we compared wild-type exogenous NEDD9 with a hybrid construct in which the NEDD9 FAT domain had been exchanged for the p130Cas (also known as BCAR1) FAT domain. Fluorescence recovery after photobleaching (FRAP) revealed significantly slowed exchange of the fusion protein at focal adhesions and significantly slower two-dimensional migration...
April 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28202658/mechanisms-for-nonmitotic-activation-of-aurora-a-at-cilia
#6
REVIEW
Vladislav Korobeynikov, Alexander Y Deneka, Erica A Golemis
Overexpression of the Aurora kinase A (AURKA) is oncogenic in many tumors. Many studies of AURKA have focused on activities of this kinase in mitosis, and elucidated the mechanisms by which AURKA activity is induced at the G2/M boundary through interactions with proteins such as TPX2 and NEDD9. These studies have informed the development of small molecule inhibitors of AURKA, of which a number are currently under preclinical and clinical assessment. While the first activities defined for AURKA were its control of centrosomal maturation and organization of the mitotic spindle, an increasing number of studies over the past decade have recognized a separate biological function of AURKA, in controlling disassembly of the primary cilium, a small organelle protruding from the cell surface that serves as a signaling platform...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28194179/the-prognostic-role-of-nedd9-and-p38-protein-expression-levels-in-urinary-bladder-transitional-cell-carcinoma
#7
Ola A Harb, Rasha Haggag, Maged M Ali, Shereen El Shorbagy, Abeer M Abdelbary, Lobna A Abdelaziz, Reham A Salim, Khaled M Abdel Wahab
Background. The most common malignant tumor of the urinary bladder is transitional cell carcinoma (TCC). Neural precursor cell-expressed developmentally downregulated protein 9 (NEDD9) is found to be a cell adhesion mediator. P38 Mitogen-Activated Protein Kinase is a serine/threonine kinases member which can mediate carcinogenesis through intracellular signaling. Methods. To assess their prognostic role; NEDD9 and p38 protein were evaluated in sections from 50 paraffin blocks of TCC. Results. The high expressions of NEDD9 and p38 protein were significantly associated with grade, stage, distant metastasis (p < 0...
2017: Journal of Oncology
https://www.readbyqxmd.com/read/28000901/identification-of-key-genes-in-colorectal-cancer-using-random-walk-with-restart
#8
Xiaofeng Cui, Kexin Shen, Zhongshi Xie, Tongjun Liu, Haishan Zhang
As the most common type of cancer and the second leading cause of cancer-associated mortality, colorectal cancer (CRC) has received increasing attention. The aim of the present study was to investigate the mechanisms of CRC by analyzing the microarray dataset, GSE32323. The GSE32323 dataset was downloaded from the Gene Expression Omnibus, and included 17 pairs of matched cancer and normal colorectal tissue samples. The differentially expressed genes (DEGs) were screened using the Linear Models for Microarray Data package and a search of CRC genes, also denoted as seed genes, was performed using the Online Mendelian Inheritance in Man database...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27974675/nedd9-may-regulate-hepatocellular-carcinoma-cell-metastasis-by-promoting-epithelial-mesenchymal-transition-and-stemness-via-repressing-smad7
#9
Zhipeng Wang, Min Shen, Peng Lu, Xiao Li, Shaojun Zhu, Shuqiang Yue
Overexpression of neural precursor cell expressed, developmentally downregulated 9 (NEDD9) is a prognostic marker of many cancers, including hepatocellular carcinoma (HCC). However, the functions and mechanisms of NEDD9 are unclear. We found that upregulation of NEDD9 promoted migration, invasion and cell-to-extracellular matrix adhesion of HCC cells. NEDD9 also induced the epithelial-mesenchymal transition (EMT) and expression of matrix metalloprotein 2 (MMP2). Increased aldehyde dehydrogenase (ALDH) activity and CD133-positive cells were observed in HCC cells with high expression of NEDD9, corresponding to greater sphere formation in cancer stem cells (CSCs)...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27916098/-knockdown-of-nedd9-inhibits-the-proliferation-invasion-and-migration-of-esophageal-carcinoma-ec109-cells
#10
Wen Zhang, Shaojun Li, Yunlong Zhao, Nannan Guo, Yingjie Li
Objective To observe the expression of the neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) in esophageal cancer, to investigate the impact of decreased expression of NEDD9 on invasion and migration, and to explicit the function of NEDD9 in EC109 human esophageal cancer cell line. Methods Immunohistochemical staining was used to detect the expression of NEDD9 in human esophageal cancer tissues and paracancerous normal tissues. RNA interfering (RNAi) was used to knockdown NEDD9 in EC109 cells...
December 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27771718/sodium-butyrate-upregulates-mir-203-expression-to-exert-anti-proliferation-effect-on-colorectal-cancer-cells
#11
Ruirui Han, Qianqian Sun, Jianbo Wu, Pengyuan Zheng, Guoqiang Zhao
BACKGROUND: As the end product of the bacterial fermentation of dietary fiber in the colonic lumen, sodium butyrate (NaBt) has been reported to exert antitumor effects on colorectal cancer (CRC). In addition to functioning as a histone deacetylase (HDAC) inhibitor, NaBt also regulates the expression of microRNAs (miRNAs) to inhibit CRC cell proliferation. Yet, the mechanisms involved are not completely understood. Here we investigate whether NaBt regulates miR-203 to inhibit CRC growth and explore the promising target gene of miR-203 in CRC cells...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27703373/the-expressions-of-nedd9-and-e-cadherin-correlate-with-metastasis-and-poor-prognosis-in-triple-negative-breast-cancer-patients
#12
Peng Li, Tingting Sun, Qingzhong Yuan, Guozheng Pan, Jian Zhang, Diwen Sun
BACKGROUND: Neural precursor cell expressed, developmentally downregulated 9 (NEDD9), a member of Crk-associated substrate family, is involved in cancer cell adhesion, migration, invasion, and epithelial-mesenchymal transition. E-cadherin is a key event in the cellular invasion during the epithelial-mesenchymal transition mechanism. The aim of this study was to evaluate the association among NEDD9 expression, E-cadherin expression, and survival in triple-negative breast cancer (TNBC) patients...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27664007/downregulation-of-nedd9-by-apigenin-suppresses-migration-invasion-and-metastasis-of-colorectal-cancer-cells
#13
Jin Dai, Peter G Van Wie, Leonard Yenwong Fai, Donghern Kim, Lei Wang, Pratheeshkumar Poyil, Jia Luo, Zhuo Zhang
Apigenin is a natural flavonoid which possesses multiple anti-cancer properties such as anti-proliferation, anti-inflammation, and anti-metastasis in many types of cancers including colorectal cancer. Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a multi-domain scaffolding protein of the Cas family which has been shown to correlate with cancer metastasis and progression. The present study investigates the role of NEDD9 in apigenin-inhibited cell migration, invasion, and metastasis of colorectal adenocarcinoma DLD1 and SW480 cells...
November 15, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27336669/identification-of-nedd9-as-a-tgf-%C3%AE-smad2-3-target-gene-involved-in-rankl-induced-osteoclastogenesis-by-comprehensive-analysis
#14
Yasunori Omata, Shinya Nakamura, Takuma Koyama, Tetsuro Yasui, Jun Hirose, Naohiro Izawa, Takumi Matsumoto, Yuuki Imai, Sachiko Seo, Mineo Kurokawa, Shuichi Tsutsumi, Yuho Kadono, Chikao Morimoto, Hiroyuki Aburatani, Takeshi Miyamoto, Sakae Tanaka
TGF-ß is a multifunctional cytokine that is involved in cell proliferation, differentiation and function. We previously reported an essential role of the TGF-ß -Smad2/3 pathways in RANKL-induced osteoclastogenesis. Using chromatin immunoprecipitation followed by sequencing, we comprehensively identified Smad2/3 target genes in bone marrow macrophages. These genes were enriched in the gene population upregulated by TGF-ß and downregulated by RANKL. Recent studies have revealed that histone modifications, such as trimethylation of histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3), critically regulate key developmental steps...
2016: PloS One
https://www.readbyqxmd.com/read/27085739/retinoic-acid-regulates-schwann-cell-migration-via-nedd9-induction-by-transcriptional-and-post-translational-mechanisms
#15
Maria-Jesus Latasa, Ana María Jiménez-Lara, Jose Miguel Cosgaya
Schwann cell migration is essential during the regenerative response to nerve injury, however, the factors that regulate this phenomenon are not yet clear. Here we describe that retinoic acid (RA), whose production and signaling activity are greatly enhanced during nerve regeneration, increases Schwann cell migration. This is accompanied by the up-regulation of NEDD9, a member of the CAS family of scaffold proteins previously implicated in migratory and invasive behavior in gliomas, melanomas and the neural crest cells from which Schwann cells derive...
July 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27078000/computational-reconstruction-of-nf%C3%AE%C2%BAb-pathway-interaction-mechanisms-during-prostate-cancer
#16
Daniela Börnigen, Svitlana Tyekucheva, Xiaodong Wang, Jennifer R Rider, Gwo-Shu Lee, Lorelei A Mucci, Christopher Sweeney, Curtis Huttenhower
Molecular research in cancer is one of the largest areas of bioinformatic investigation, but it remains a challenge to understand biomolecular mechanisms in cancer-related pathways from high-throughput genomic data. This includes the Nuclear-factor-kappa-B (NFκB) pathway, which is central to the inflammatory response and cell proliferation in prostate cancer development and progression. Despite close scrutiny and a deep understanding of many of its members' biomolecular activities, the current list of pathway members and a systems-level understanding of their interactions remains incomplete...
April 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/26968260/regulation-of-melanoma-progression-through-the-tcf4-mir-125b-nedd9-cascade
#17
Florian Rambow, Audrey Bechadergue, Flavie Luciani, Gwendoline Gros, Melanie Domingues, Jacky Bonaventure, Guillaume Meurice, Jean-Christophe Marine, Lionel Larue
Melanoma progression from a primary lesion to a distant metastasis is a complex process associated with genetic alterations, epigenetic modifications, and phenotypic switches. Elucidation of these phenomena may indicate how to interfere with this fatal disease. The role of microRNAs as key negative regulators of gene expression, controlling all cellular processes including cell migration and invasion, is now being recognized. Here, we used in silico analysis of microRNA expression profiles of primary and metastatic melanomas and functional experiments to show that microRNA-125b (miR-125b) is a determinant candidate of melanoma progression: (i) miR-125b is more strongly expressed in aggressive metastatic than primary melanomas, (ii) there is an inverse correlation between the amount of miR-125b and overall patient survival, (iii) invasion/migration potentials in vitro are inversely correlated with the amount of miR-125b in a series of human melanoma cell lines, and (iv) inhibition of miR-125b reduces migratory and invasive potentials without affecting cell proliferation in vitro...
June 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/26844528/oncogenic-driver-genes-and-the-inflammatory-microenvironment-dictate-liver-tumor-phenotype
#18
Matthias S Matter, Jens U Marquardt, Jesper B Andersen, Cristina Quintavalle, Nikolay Korokhov, Jim K Stauffer, Kosuke Kaji, Thomas Decaens, Luca Quagliata, Fathi Elloumi, Tanya Hoang, Alfredo Molinolo, Elizabeth A Conner, Achim Weber, Mathias Heikenwalder, Valentina M Factor, Snorri S Thorgeirsson
UNLABELLED: The majority of hepatocellular carcinoma develops in the background of chronic liver inflammation caused by viral hepatitis and alcoholic or nonalcoholic steatohepatitis. However, the impact of different types of chronic inflammatory microenvironments on the phenotypes of tumors generated by distinct oncogenes is largely unresolved. To address this issue, we generated murine liver tumors by constitutively active AKT-1 (AKT) and β-catenin (CAT), followed by induction of chronic liver inflammation by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and carbon tetrachloride...
June 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/26701889/aberrant-nrp-1-expression-serves-as-predicator-of-metastatic-endometrial-and-lung-cancers
#19
COMPARATIVE STUDY
Imoh S Okon, Ye Ding, Kathleen A Coughlan, Qiongxin Wang, Ping Song, Doris M Benbrook, Ming-Hui Zou
Neuropilin-1 (NRP-1) has emerged as an important driver of tumor-promoting phenotypes of human malignancies. However, incomplete knowledge exists as to how this single-pass transmembrane receptor mediates pleiotropic tumor-promoting functions. The purpose of this study was to evaluate NRP-1 expression and metastatic properties in 94 endometrial cancer and matching serum specimens and in a lung cancer cell line. We found that NRP-1 expression significantly correlated with increased tumoral expression of vascular endothelial growth factor 2 (VEGFR2) and serum levels of hepatocyte growth factor (HGF) and cell growth-stimulating factor (C-GSF)...
February 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/26683084/mice-null-for-nedd9-hef1%C3%AE-display-extensive-hippocampal-dendritic-spine-loss-and-cognitive-impairment
#20
D C Knutson, A M Mitzey, L E Talton, M Clagett-Dame
NEDD9 (neural precursor cell expressed, developmentally down-regulated 9) is a member of the CAS (Crk-associated substrate) family of scaffolding proteins that regulate cell adhesion and migration. A Nedd9 knock-out/lacZ knock-in mouse (Nedd9(-/)(-)) was developed in order to study Nedd9 expression and function in the nervous system. Herein we show that NEDD9 is expressed in the adult brain and is prominently expressed in the hippocampus. Behavioral testing uncovered functional deficits in Nedd9(-)(/)(-) mice...
February 1, 2016: Brain Research
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