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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
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)...
December 10, 2016: Oncotarget
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
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
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
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...
September 20, 2016: Toxicology and Applied Pharmacology
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
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
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
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
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
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
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
Harsh B Pathak, Yan Zhou, Geetika Sethi, Jeff Hirst, Russell J Schilder, Erica A Golemis, Andrew K Godwin
Molecular targeted therapies have been the focus of recent clinical trials for the treatment of patients with recurrent epithelial ovarian cancer (EOC). The majority have not fared well as monotherapies for improving survival of these patients. Poor bioavailability, lack of predictive biomarkers, and the presence of multiple survival pathways can all diminish the success of a targeted agent. Dasatinib is a tyrosine kinase inhibitor of the Src-family kinases (SFK) and in preclinical studies shown to have substantial activity in EOC...
2015: PloS One
Parvez Syed, Shabarni Gupta, Saket Choudhary, Narendra Goud Pandala, Apurva Atak, Annie Richharia, Manubhai K P, Heng Zhu, Sridhar Epari, Santosh B Noronha, Aliasgar Moiyadi, Sanjeeva Srivastava
The heterogeneity and poor prognosis associated with gliomas, makes biomarker identification imperative. Here, we report autoantibody signatures across various grades of glioma serum samples and sub-categories of glioblastoma multiforme using Human Proteome chips containing ~17000 full-length human proteins. The deduced sets of classifier proteins helped to distinguish Grade II, III and IV samples from the healthy subjects with 88, 89 and 94% sensitivity and 87, 100 and 73% specificity, respectively. Proteins namely, SNX1, EYA1, PQBP1 and IGHG1 showed dysregulation across various grades...
2015: Scientific Reports
Jue Wang, Wen-Juan Yang, Chao Sun, Yun Luan, Guang-Hui Cheng, Kai-Lin Li, Feng Kong
Renal cell carcinoma (RCC) is the most lethal of all genitourinary malignancies. NEDD9/HEF1/Cas-L is a member of the Cas protein family and is known as a biomarker in multiple cancer types. In this study, we demonstrate for the first time that NEDD9 was upregulated in RCC tissue and cell lines. Immunohistochemical analysis and quantitative RT-PCR analysis showed low expression of NEDD9 in normal renal tissues and high expression in RCC tissues. In addition, in vitro experiments show that expression of NEDD9 was upregulated in RCC cell lines...
2014: Oncology Research
Sisen Zhang, Lihua Wu
Neural precursor cell expressed, developmentally downregulated 9 (NEDD9), a gene exclusively expressed in the brain during embryonic stages but not in brains of adult mice, is an important cytoskeletal protein and regarded as a 'router/hub' in cellular signal transduction processes connecting external stimulation signals with downstream target proteins that can directly promote tumor metastasis. Numerous studies showed that NEDD9 has an essential role in cell proliferation, apoptosis, adhesion, migration and invasion...
November 2015: Molecular Medicine Reports
Mehmet Karabulut, Halil Alis, Cigdem Usul Afsar, Senem Karabulut, Ali Kocatas, Hilal Oguz, Nuri Faruk Aykan
BACKGROUND: Neural precursor cell-expressed, developmentally down regulated 9 (NEDD9), a member of Crk-associated substrate (CAS) family, is highly expressed in multiple cancer types and involved in cancer cell adhesion, migration and invasion. The prognostic value of NEDD9 has been evaluated before and its expression is a predictor of poor prognosis in cancer patients. The objective of this study was to determine the clinical significance of the serum levels of NEDD9 in gastric cancer (GC) patients...
July 2015: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Alexander Deneka, Vladislav Korobeynikov, Erica A Golemis
The CAS (Crk-associated substrate) adaptor protein family consists of four members: CASS1/BCAR1/p130Cas, CASS2/NEDD9/HEF1/Cas-L, CASS3/EFS/Sin and CASS4/HEPL. While CAS proteins lack enzymatic activity, they contain specific recognition and binding sites for assembly of larger signaling complexes that are essential for cell proliferation, survival, migration, and other processes. All family members are intermediates in integrin-dependent signaling pathways mediated at focal adhesions, and associate with FAK and SRC family kinases to activate downstream effectors regulating the actin cytoskeleton...
October 1, 2015: Gene
Bénédicte Rousseau, Catherine Jacquot, Julie Le Palabe, Marine Malleter, Christophe Tomasoni, Tifenn Boutard, Vehary Sakanyan, Christos Roussakis
Lung cancer is a serious public health problem. Although there has been significant progress in chemotherapy, non-small cell lung cancer is still resistant to current treatments, primarily because of the slow rate of cell development. It is thus important to find new molecules directed against targets other than proliferation agents. Considering the high proportion of mutant proteins in tumor cells, and the high rate of mutation of the TP53 gene in all cancers, and in NSCLC in particular, this gene is a perfect target...
2015: Scientific Reports
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