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centrosome amplification

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https://www.readbyqxmd.com/read/28515047/centrosome-amplification-a-suspect-in-breast-cancer-and-racial-disparities
#1
Angela Ogden, Padmashree C G Rida, Ritu Aneja
The multifaceted involvement of centrosome amplification (CA) in tumorigenesis is coming into focus following years of meticulous experimentation, which have elucidated the powerful abilities of CA to promote cellular invasion, disrupt stem cell division, drive chromosomal instability (CIN), and perturb tissue architecture, activities that can accelerate tumor progression. Integration of the extant in vitro, in vivo, and clinical data suggests that in some tissues CA may be a tumor-initiating event, in others a consequential "hit" in multistep tumorigenesis, and in still others non-tumorigenic...
May 17, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28454331/centrosome-amplification-in-chondrosarcomas-a-primary-cell-culture-and-cryopreserved-tumor-sample-study
#2
Carla Aparecida Pinheiro, Iberê Cauduro Soares, Valter Penna, Jeremy Squire, Rui Manuel Vieira Reis, Sandra Regina Morini da Silva, Isabela de Carvalho, Marjori Leiva Camparoto, Maicon Fernando Zanon da Silva, Adhemar Longatto Longatto Filho
The genetics background underlying the aggressiveness of chondrosarcoma (CS) is poorly understood. One possible cause of malignant transformation is chromosomal instability, which involves an error in mitotic segregation due to numerical and/or functional abnormalities of centrosomes. The present study aimed to evaluate centrosome amplification in cryopreserved samples of tumor tissue from patients with CS. An analysis was performed on 3 primary cultures of tumors from patients who underwent surgery between January 2012 and December 2012 at the Department of Orthopedics at the Barretos Cancer Hospital (Barretos, Brazil)...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28415605/kifc1-is-essential-for-acrosome-formation-and-nuclear-shaping-during-spermiogenesis-in-the-lobster-procambarus-clarkii
#3
Dan-Dan Ma, Lian Bi, Wan-Xi Yang
In order to study the function of kinesin-14 motor protein KIFC1 during spermatogenesis of Procambarus clarkii, the full length of kifc1 was cloned from testes cDNA using Rapid-Amplification of cDNA Ends (RACE). The deduced KIFC1 protein sequence showed the highest similarity between Procambarus clarkii and Eriocheir senensis (similarity rate as 64%). According to the results of in situ hybridization (ISH), the kifc1 mRNA was gathered in the acrosome location above nucleus in the mid- and late-stage spermatids...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402684/a-nonsense-alms1-mutation-underlies-alstr%C3%A3-m-syndrome-in-an-extended-mennonite-kindred-settled-in-north-mexico
#4
Marisa Cruz-Aguilar, Carlos Galaviz-Hernández, José Hiebert-Froese, Martha Sosa-Macías, Juan Carlos Zenteno
AIM: Alström syndrome (AS) is a rare autosomal recessive multisystem disease caused by biallelic mutations in ALMS1, a gene encoding a widely expressed centrosomal/basal body protein. Although more than 200 pathogenic mutations in ALMS1 have been identified to date in AS patients from various ethnic populations, there are very few reports of ALMS1 founder mutations in isolated populations. Our aim was to describe the molecular characterization of an isolate of AS patients from an extended inbred Mennonite kindred settled in Mexico...
April 12, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28385950/the-daughter-centriole-controls-ciliogenesis-by-regulating-neurl-4-localization-at-the-centrosome
#5
Abdelhalim Loukil, Kati Tormanen, Christine Sütterlin
The two centrioles of the centrosome differ in age and function. Although the mother centriole mediates most centrosome-dependent processes, the role of the daughter remains poorly understood. A recent study has implicated the daughter centriole in centriole amplification in multiciliated cells, but its contribution to primary ciliogenesis is unclear. We found that manipulations that prevent daughter centriole formation or induce its separation from the mother abolish ciliogenesis. This defect was caused by stabilization of the negative ciliogenesis regulator CP110 and was corrected by CP110 depletion...
May 1, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28361952/usp9x-regulates-centrosome-duplication-and-promotes-breast-carcinogenesis
#6
Xin Li, Nan Song, Ling Liu, Xinhua Liu, Xiang Ding, Xin Song, Shangda Yang, Lin Shan, Xing Zhou, Dongxue Su, Yue Wang, Qi Zhang, Cheng Cao, Shuai Ma, Na Yu, Fuquan Yang, Yan Wang, Zhi Yao, Yongfeng Shang, Lei Shi
Defective centrosome duplication is implicated in microcephaly and primordial dwarfism as well as various ciliopathies and cancers. Yet, how the centrosome biogenesis is regulated remains poorly understood. Here we report that the X-linked deubiquitinase USP9X is physically associated with centriolar satellite protein CEP131, thereby stabilizing CEP131 through its deubiquitinase activity. We demonstrate that USP9X is an integral component of centrosome and is required for centrosome biogenesis. Loss-of-function of USP9X impairs centrosome duplication and gain-of-function of USP9X promotes centrosome amplification and chromosome instability...
March 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28325915/prognostic-value-of-ca20-a-score-based-on-centrosome-amplification-associated-genes-in-breast-tumors
#7
Angela Ogden, Padmashree C G Rida, Ritu Aneja
Centrosome amplification (CA) is a hallmark of cancer, observable in ≥75% of breast tumors. CA drives aggressive cellular phenotypes such as chromosomal instability (CIN) and invasiveness. Thus, assessment of CA may offer insights into the prognosis of breast cancer and identify patients who might benefit from centrosome declustering agents. However, it remains unclear whether CA is correlated with clinical outcomes after adjusting for confounding factors. To gain insights, we developed a signature, "CA20", comprising centrosome structural genes and genes whose dysregulation is implicated in inducing CA...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28284839/depletion-of-tumor-suppressor-kank1-induces-centrosomal-amplification-via-hyperactivation-of-rhoa
#8
Jun-Ichiro Suzuki, Badal Chandra Roy, Takunori Ogaeri, Naoto Kakinuma, Ryoiti Kiyama
Chromosome instability, frequently found in cancer cells, is caused by a deficiency in cell division, including centrosomal amplification and cytokinesis failure, and can result in abnormal chromosome content or aneuploidy. The small GTPase pathways have been implicated as important processes in cell division. We found that knockdown of a tumor suppressor protein Kank1 increases the number of cells with a micronucleus or bi-/multi-nuclei, which was likely caused by centrosomal amplification. Kank1 interacts with Daam1, known to bind to and activate a small GTPase, RhoA, in actin assembly...
March 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28277612/wdr62-overexpression-is-associated-with-a-poor-prognosis-in-patients-with-lung-adenocarcinoma
#9
Kazuya Shinmura, Hisami Kato, Yuichi Kawanishi, Hisaki Igarashi, Yusuke Inoue, Katsuhiro Yoshimura, Satoki Nakamura, Hidehiko Fujita, Kazuhito Funai, Masayuki Tanahashi, Hiroshi Niwa, Hiroshi Ogawa, Haruhiko Sugimura
Human WDR62, which is localized in the cytoplasm including the centrosome, is known to be responsible for primary microcephaly; however, the role of WDR62 abnormality in cancers remains largely unknown. In this study, we aimed to reveal the pathological role of WDR62 abnormality in lung adenocarcinoma (LAC). We first examined the WDR62 mRNA expression level of LAC (n = 64) using a QRT-PCR analysis and found that WDR62 mRNA transcripts were significantly overexpressed in LAC (P = 0.0432, Wilcoxon matched pairs test)...
March 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28186092/epstein-barr-virus-particles-induce-centrosome-amplification-and-chromosomal-instability
#10
Anatoliy Shumilov, Ming-Han Tsai, Yvonne T Schlosser, Anne-Sophie Kratz, Katharina Bernhardt, Susanne Fink, Tuba Mizani, Xiaochen Lin, Anna Jauch, Josef Mautner, Annette Kopp-Schneider, Regina Feederle, Ingrid Hoffmann, Henri-Jacques Delecluse
Infections with Epstein-Barr virus (EBV) are associated with cancer development, and EBV lytic replication (the process that generates virus progeny) is a strong risk factor for some cancer types. Here we report that EBV infection of B-lymphocytes (in vitro and in a mouse model) leads to an increased rate of centrosome amplification, associated with chromosomal instability. This effect can be reproduced with virus-like particles devoid of EBV DNA, but not with defective virus-like particles that cannot infect host cells...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28171744/centrosome-amplification-and-cancer-a-question-of-sufficiency
#11
Jordan W Raff, Renata Basto
Centrosome amplification is a common feature of many types of cancer, but whether it is a cause or consequence is hotly debated. In this issue of Developmental Cell, Levine et al. (2017) provide strong evidence that centrosome amplification is sufficient to initiate tumorigenesis in a mouse model.
February 6, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28148738/cell-scientist-to-watch-andrew-holland
#12
(no author information available yet)
Andrew received his first degree in natural sciences from the University of Cambridge and a Masters degree from the University of Manchester, followed by a PhD with Stephen Taylor in Manchester. He then moved to California in 2007 with an EMBO long-term fellowship for his postdoctoral research with Don Cleveland at the Ludwig Institute for Cancer Research. In 2013, Andrew started his own lab as an Assistant Professor in the Department of Molecular Biology and Genetics at the Johns Hopkins University School of Medicine, having been named a Kimmel Scholar and a Pew-Stewart Scholar in 2014...
February 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28132847/centrosome-amplification-is-sufficient-to-promote-spontaneous-tumorigenesis-in-mammals
#13
Michelle S Levine, Bjorn Bakker, Bram Boeckx, Julia Moyett, James Lu, Benjamin Vitre, Diana C Spierings, Peter M Lansdorp, Don W Cleveland, Diether Lambrechts, Floris Foijer, Andrew J Holland
Centrosome amplification is a common feature of human tumors, but whether this is a cause or a consequence of cancer remains unclear. Here, we test the consequence of centrosome amplification by creating mice in which centrosome number can be chronically increased in the absence of additional genetic defects. We show that increasing centrosome number elevated tumor initiation in a mouse model of intestinal neoplasia. Most importantly, we demonstrate that supernumerary centrosomes are sufficient to drive aneuploidy and the development of spontaneous tumors in multiple tissues...
February 6, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28104305/cp39-cp75-and-cp91-are-major-structural-components-of-the-dictyostelium-centrosome-s-core-structure
#14
Irene Meyer, Tatjana Peter, Petros Batsios, Oliver Kuhnert, Anne Krüger-Genge, Carl Camurça, Ralph Gräf
The acentriolar Dictyostelium centrosome is a nucleus-associated body consisting of a core structure with three plaque-like layers, which are surrounded by a microtubule-nucleating corona. The core duplicates once per cell cycle at the G2/M transition, whereby its central layer disappears and the two outer layers form the mitotic spindle poles. Through proteomic analysis of isolated centrosomes, we have identified CP39 and CP75, two essential components of the core structure. Both proteins can be assigned to the central core layer as their centrosomal presence is correlated to the disappearance and reappearance of the central core layer in the course of centrosome duplication...
March 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28100636/centriole-splitting-caused-by-loss-of-the-centrosomal-linker-protein-c-nap1-reduces%C3%A2-centriolar-satellite-density-and-impedes%C3%A2-centrosome-amplification
#15
Anne-Marie Flanagan, Elena Stavenschi, Shivakumar Basavaraju, David Gaboriau, David A Hoey, Ciaran G Morrison
Duplication of the centrosomes is a tightly regulated process. Abnormal centrosome numbers can impair cell division and cause changes in how cells migrate. Duplicated centrosomes are held together by a proteinaceous linker made up of rootletin filaments anchored to the centrioles by C-NAP1. This linker is removed in a NEK2A kinase-dependent manner as mitosis begins. To explore C-NAP1 activities in regulating centrosome activities, we used genome editing to ablate it. C-NAP1-null cells were viable and had an increased frequency of premature centriole separation, accompanied by reduced density of the centriolar satellites, with reexpression of C-NAP1 rescuing both phenotypes...
March 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28063737/discovery-of-centrosomal-protein-70-as-an-important-player-in-the-development-and-progression-of-breast-cancer
#16
Xingjuan Shi, Dengwen Li, Yujue Wang, Shiyu Liu, Juan Qin, Jun Wang, Jie Ran, Yu Zhang, Qinghai Huang, Xiangdong Liu, Jun Zhou, Min Liu
Centrosome abnormalities have been implicated in the development and progression of breast cancer. However, the molecular players involved in the above processes remain largely uncharacterized. Herein, we identify centrosomal protein 70 (Cep70) as an important factor that mediates breast cancer growth and metastasis. Cep70 is up-regulated in breast cancer tissues and cell lines, and its expression is closely correlated with several clinicopathologic variables associated with breast cancer progression. Mechanistic studies reveal that the up-regulation of Cep70 in breast cancer occurs at the mRNA level and is independent of gene amplification...
March 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28008224/centrosome-a-promising-anti-cancer-target
#17
REVIEW
Yainyrette Rivera-Rivera, Harold I Saavedra
The centrosome, an organelle discovered >100 years ago, is the main microtubule-organizing center in mammalian organisms. The centrosome is composed of a pair of centrioles surrounded by the pericentriolar material (PMC) and plays a major role in the regulation of cell cycle transitions (G1-S, G2-M, and metaphase-anaphase), ensuring the normality of cell division. Hundreds of proteins found in the centrosome exert a variety of roles, including microtubule dynamics, nucleation, and kinetochore-microtubule attachments that allow correct chromosome alignment and segregation...
2016: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/27998958/bisphenol-a-and-its-analogues-disrupt-centrosome-cycle-and-microtubule-dynamics-in-prostate-cancer
#18
Shuk-Mei Ho, Rahul Rao, Sarah To, Emma Schoch, Pheruza Tarapore
Humans are increasingly exposed to structural analogues of bisphenol A (BPA), as BPA is being replaced by these compounds in BPA-free consumer products. We have previously shown that chronic and developmental exposure to BPA is associated with increased prostate cancer (PCa) risk in human and animal models. Here, we examine whether exposure of PCa cells (LNCaP, C4-2) to low-dose BPA and its structural analogues (BPS, BPF, BPAF, TBBPA, DMBPA and TMBPA) affects centrosome amplification (CA), a hallmark of cancer initiation and progression...
February 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/27926524/selective-hdac-inhibition-by-acy-241-enhances-the-activity-of-paclitaxel-in-solid-tumor-models
#19
Pengyu Huang, Ingrid Almeciga-Pinto, Matthew Jarpe, John H van Duzer, Ralph Mazitschek, Min Yang, Simon S Jones, Steven N Quayle
ACY-241 is a novel, orally available and selective histone deacetylase (HDAC) 6 inhibitor in Phase 1b clinical development in multiple myeloma (NCT 02400242). Like the structurally related drug ACY-1215 (ricolinostat), ACY-241 has the potential for a substantially reduced side effect profile versus current nonselective HDAC inhibitor drug candidates due to reduced potency against Class I HDACs while retaining the potential for anticancer effectiveness. We now show that combination treatment of xenograft models with paclitaxel and either ricolinostat or ACY-241 significantly suppresses solid tumor growth...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27924065/the-more-the-messier-centrosome-amplification-as-a-novel-biomarker-for-personalized-treatment-of-colorectal-cancers
#20
REVIEW
Monica M Mahathre, Padmashree Cg Rida, Ritu Aneja
Colon cancer is currently the third most common cancer and second most fatal cancer in the United States, resulting in approximately 600,000 deaths annually. Though colorectal cancer death rates are decreasing by about 3% every year, disease outcomes could be substantially improved with more research into the drivers of colon carcinogenesis, the determinants of aggressiveness in colorectal cancer and the identification of biomarkers that could enable choice of more optimal treatments. Colon carcinogenesis is notably a slow process that can take decades...
November 2016: Journal of Biomedical Research
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