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centrosome amplification

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https://www.readbyqxmd.com/read/29792311/pedf-regulates-plasticity-of-a-novel-lipid-mtoc-axis-in-prostate-cancer-associated-fibroblasts
#1
Francesca Nardi, Philip Fitchev, Omar E Franco, Jelena Ivanisevic, Adrian Scheibler, Simon W Hayward, Charles B Brendler, Michael A Welte, Susan E Crawford
Prostate tumors make metabolic adaptations to ensure adequate energy and amplify cell cycle regulators such as centrosomes to sustain their proliferative capacity. It is not known whether cancer associated fibroblasts (CAFs) undergo metabolic re-programming. We postulated that CAFs augment lipid storage and amplify centrosomal or non-centrosomal microtubule organizing centers (MTOCs) through a pigment epithelium-derived factor (PEDF)-dependent lipid-MTOC signaling axis. Primary normal human prostate fibroblasts (NFs) and CAFs were evaluated for lipid content, triacylglycerol-regulating proteins, MTOC number and distribution...
May 23, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29769406/spindle-assembly-disruption-and-cancer-cell-apoptosis-with-a-cltc-binding-compound
#2
Michael J Bond, Marina Bleiler, Lauren E Harrison, Eric W Scocchera, Masako Nakanishi, Narendran G-Dayanandan, Santosh Keshipeddy, Daniel W Rosenberg, Dennis L Wright, Charles Giardina
AK3 compounds are mitotic-arrest agents that induce high levels of γH2AX during mitosis and apoptosis following release from arrest. We synthesized a potent AK3 derivative, AK306, that induced arrest and apoptosis of the HCT116 colon cancer cell line with an EC50 of ~50 nM. AK306 was active on a broad spectrum of cancer cell lines with total growth inhibition values ranging from ~25 nM to 25 µM. Using biotin and BODIPY-linked derivatives of AK306, binding to clathrin heavy chain (CLTC/CHC) was observed, a protein with roles in endocytosis and mitosis...
May 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29768267/type-2-diabetes-promotes-cell-centrosome-amplification-via-akt-ros-dependent-signalling-of-rock1-and-14-3-3%C3%AF
#3
Pu Wang, Yu Cheng Lu, Jie Wang, Lan Wang, Hanry Yu, Yuan Fei Li, Alice Kong, Juliana Chan, Shaochin Lee
BACKGROUND/AIMS: Type 2 diabetes is associated with oxidative stress and DNA damage which can cause centrosome amplification. Thus, the study investigated centrosome amplification in type 2 diabetes and the underlying mechanisms. METHODS: Centrosome numbers in human peripheral blood mononuclear blood cells (PBMC) from healthy subjects and patients with type 2 diabetes were compared to access the association between type 2 diabetes and centrosome amplification. Colon cancer cells were used to investigate the molecular mechanisms underlying the centrosome amplification triggered by high glucose, insulin and palmitic acid...
May 11, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29739803/centrosome-amplification-arises-before-neoplasia-and-increases-upon-p53-loss-in-tumorigenesis
#4
Carla A M Lopes, Marta Mesquita, Ana Isabel Cunha, Joana Cardoso, Sara Carapeta, Cátia Laranjeira, António E Pinto, José B Pereira-Leal, António Dias-Pereira, Mónica Bettencourt-Dias, Paula Chaves
Centrosome abnormalities are a typical hallmark of human cancers. However, the origin and dynamics of such abnormalities in human cancer are not known. In this study, we examined centrosomes in Barrett's esophagus tumorigenesis, a well-characterized multistep pathway of progression, from the premalignant condition to the metastatic disease. This human cancer model allows the study of sequential steps of progression within the same patient and has representative cell lines from all stages of disease. Remarkably, centrosome amplification was detected as early as the premalignant condition and was significantly expanded in dysplasia...
May 8, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29719584/-drosophila-pebp1-inhibits-intestinal-stem-cell-aging-via-suppression-of-erk-pathway
#5
Jung-Hoon Pyo, Ho-Jun Jeon, Joung-Sun Park, Jae-Sun Lee, Hae-Young Chung, Mi-Ae Yoo
The intestine is a high cellular turnover tissue largely dependent on the regenerative function of stem cell throughout life, and a signaling center for the health and viability of organisms. Therefore, better understanding of the mechanisms underlying the regulation of intestinal stem cell (ISC) regenerative potential is essential for the possible intervention of aging process and age-related diseases. Drosophila midgut is a well-established model system for studying the mechanisms underlying ISC regenerative potential during aging...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29706521/chromosome-segregation-is-biased-by-kinetochore-size
#6
Danica Drpic, Ana C Almeida, Paulo Aguiar, Fioranna Renda, Joana Damas, Harris A Lewin, Denis M Larkin, Alexey Khodjakov, Helder Maiato
Chromosome missegregation during mitosis or meiosis is a hallmark of cancer and the main cause of prenatal death in humans. The gain or loss of specific chromosomes is thought to be random, with cell viability being essentially determined by selection. Several established pathways including centrosome amplification, sister-chromatid cohesion defects, or a compromised spindle assembly checkpoint can lead to chromosome missegregation. However, how specific intrinsic features of the kinetochore-the critical chromosomal interface with spindle microtubules-impact chromosome segregation remains poorly understood...
April 20, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29683733/cep55-overexpression-causes-male-specific-sterility-in-mice-by-suppressing-foxo1-nuclear-retention-through-sustained-activation-of-pi3k-akt-signaling
#7
Debottam Sinha, Murugan Kalimutho, Josephine Bowles, Ai-Leen Chan, D Jo Merriner, Amanda L Bain, Jacinta L Simmons, Raimundo Freire, J Alejandro Lopez, Robin M Hobbs, Moira K O'Bryan, Kum Kum Khanna
Spermatogenesis is a dynamic process involving self-renewal and differentiation of spermatogonial stem cells, meiosis, and ultimately, the differentiation of haploid spermatids into sperm. Centrosomal protein (CEP)-55 is necessary for somatic cell abscission during cytokinesis. It facilitates equal segregation of cytoplasmic contents between daughter cells by recruiting endosomal sorting complex required for transport machinery (ESCRT) at the midbody. In germ cells, CEP55, in partnership with testes expressed-14 protein (TEX14), has also been shown to be an integral component of intercellular bridge before meiosis...
April 17, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29682766/non-cell-cycle-functions-of-the-cdk-network-in-ciliogenesis-recycling-the-cell-cycle-oscillator
#8
REVIEW
Liliana Krasinska, Daniel Fisher
Cyclin-dependent kinases are Ser/Thr protein kinases best known for their cell cycle roles, where CDK1 triggers mitotic onset in all eukaryotes. CDKs are also involved in various other cellular processes, some of which, such as transcription and centrosome duplication, are coupled to cell cycle progression. A new study suggests that the mitotic CDK network is active at low levels in non-dividing, differentiating precursors of multiciliated cells, and that it drives ciliogenesis. Manipulating the activity of CDK1 or PLK1 altered transitions between the amplification, growth, and disengagement phases, in a manner analogous to the control of passage through different phases of mitosis...
April 23, 2018: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/29593297/over-elongation-of-centrioles-in-cancer-promotes-centriole-amplification-and-chromosome-missegregation
#9
Gaëlle Marteil, Adan Guerrero, André F Vieira, Bernardo P de Almeida, Pedro Machado, Susana Mendonça, Marta Mesquita, Beth Villarreal, Irina Fonseca, Maria E Francia, Katharina Dores, Nuno P Martins, Swadhin C Jana, Erin M Tranfield, Nuno L Barbosa-Morais, Joana Paredes, David Pellman, Susana A Godinho, Mónica Bettencourt-Dias
Centrosomes are the major microtubule organising centres of animal cells. Deregulation in their number occurs in cancer and was shown to trigger tumorigenesis in mice. However, the incidence, consequence and origins of this abnormality are poorly understood. Here, we screened the NCI-60 panel of human cancer cell lines to systematically analyse centriole number and structure. Our screen shows that centriole amplification is widespread in cancer cell lines and highly prevalent in aggressive breast carcinomas...
March 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/29535384/integrated-genomics-and-functional-validation-identifies-malignant-cell-specific-dependencies-in-triple-negative-breast-cancer
#10
Nirmesh Patel, Daniel Weekes, Konstantinos Drosopoulos, Patrycja Gazinska, Elodie Noel, Mamun Rashid, Hasan Mirza, Jelmar Quist, Fara Brasó-Maristany, Sumi Mathew, Riccardo Ferro, Ana Mendes Pereira, Cynthia Prince, Farzana Noor, Erika Francesch-Domenech, Rebecca Marlow, Emanuele de Rinaldis, Anita Grigoriadis, Spiros Linardopoulos, Pierfrancesco Marra, Andrew N J Tutt
Triple negative breast cancers (TNBCs) lack recurrent targetable driver mutations but demonstrate frequent copy number aberrations (CNAs). Here, we describe an integrative genomic and RNAi-based approach that identifies and validates gene addictions in TNBCs. CNAs and gene expression alterations are integrated and genes scored for pre-specified target features revealing 130 candidate genes. We test functional dependence on each of these genes using RNAi in breast cancer and non-malignant cells, validating malignant cell selective dependence upon 37 of 130 genes...
March 13, 2018: Nature Communications
https://www.readbyqxmd.com/read/29514136/deficiency-in-dna-damage-response-of-enterocytes-accelerates-intestinal-stem-cell-aging-in-drosophila
#11
Joung-Sun Park, Ho-Jun Jeon, Jung-Hoon Pyo, Young-Shin Kim, Mi-Ae Yoo
Stem cell dysfunction is closely linked to tissue and organismal aging and age-related diseases, and heavily influenced by the niche cells' environment. The DNA damage response (DDR) is a key pathway for tissue degeneration and organismal aging; however, the precise protective role of DDR in stem cell/niche aging is unclear. The Drosophila midgut is an excellent model to study the biology of stem cell/niche aging because of its easy genetic manipulation and its short lifespan. Here, we showed that deficiency of DDR in Drosophila enterocytes (ECs) accelerates intestinal stem cell (ISC) aging...
March 7, 2018: Aging
https://www.readbyqxmd.com/read/29496445/deficiency-of-atg6-impairs-beneficial-effect-of-metformin-on-intestinal-stem-cell-aging-in-drosophila
#12
Hyun-Jin Na, Jung-Hoon Pyo, Ho-Jun Jeon, Joung-Sun Park, Hae-Young Chung, Mi-Ae Yoo
Age-related changes of adult stem cell are crucial for tissue aging and age-related diseases. Thus, clarifying mechanisms to prevent adult stem cell aging is indispensable for healthy aging. Metformin, a drug for type 2 diabetes, has been highlighted for its anti-aging and anti-cancer effect. In Drosophila intestinal stem cell (ISC), we previously reported the inhibitory effect of metformin on age-related phenotypes of ISC. Here, we showed that knockdown of Atg6, a crucial autophagy-related factor, in ISC induces age-related phenotypes of ISC such as hyperproliferation, centrosome amplification, and DNA damage accumulation...
March 25, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29445034/the-skp1-cullin-f-box-e3-ligase-%C3%AE-trcp-and-cdk2-cooperate-to-control-stil-abundance-and-centriole-number
#13
Christian Arquint, Fabien Cubizolles, Agathe Morand, Alexander Schmidt, Erich A Nigg
Deregulation of centriole duplication has been implicated in cancer and primary microcephaly. Accordingly, it is important to understand how key centriole duplication factors are regulated. E3 ubiquitin ligases have been implicated in controlling the levels of several duplication factors, including PLK4, STIL and SAS-6, but the precise mechanisms ensuring centriole homeostasis remain to be fully understood. Here, we have combined proteomics approaches with the use of MLN4924, a generic inhibitor of SCF E3 ubiquitin ligases, to monitor changes in the cellular abundance of centriole duplication factors...
February 2018: Open Biology
https://www.readbyqxmd.com/read/29393405/aurora-a-overexpression-is-linked-to-development-of-aggressive-teratomas-derived-from-human-ips-cells
#14
Seiga Ohmine, Jeffrey L Salisbury, James Ingle, Giuseppe Pettinato, Candace L Haddox, Tufia Haddad, Evanthia Galanis, Yasuhiro Ikeda, Antonino B D'assoro
The discovery of human induced pluripotent stem cells (hiPSCs) is a promising advancement in the field of regenerative and personalized medicine. Expression of SOX2, KLF4, OCT4 and MYC transcription factors induces the nuclear reprogramming of somatic cells into hiPSCs that share striking similarities with human embryonic stem cells (hESCs). However, several studies have demonstrated that hESCs and hiPSCs could lead to teratoma formation in vivo, thus limiting their current clinical applications. Aberrant cell cycle regulation of hESCs is linked to centrosome amplification, which may account, for their enhanced chromosomal instability (CIN), and thus increase their tumorigenicity...
April 2018: Oncology Reports
https://www.readbyqxmd.com/read/29387975/a-comprehensive-analysis-of-brca2-gene-focus-on-mechanistic-aspects-of-its-functions-spectrum-of-deleterious-mutations-and-therapeutic-strategies-targeting-brca2-deficient-tumors
#15
Anjali Shailani, Raman Preet Kaur, Anjana Munshi
BRCA2is the main susceptibility gene known to be involved in the pathogenesis of breast cancer. It plays an important role in maintaining the genome stability by homologous recombination through DNA double-strand breaks repairing, by interacting with various other proteins including RAD51, DSS1, RPA, MRE11, PALB2, and p53. BRCA2-deficient cells show the abnormalities of chromosome number. BRCA2 is also found to be involved in centrosome duplication specifically in the metaphase to anaphase transition. Inactivation or depletion of BRCA2 leads to centrosome amplification that results in unequal separation of chromosomes...
January 31, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29370237/increased-separase-activity-and-occurrence-of-centrosome-aberrations-concur-with-transformation-of-mds
#16
Sabrina Ruppenthal, Helga Kleiner, Florian Nolte, Alice Fabarius, Wolf-Karsten Hofmann, Daniel Nowak, Wolfgang Seifarth
ESPL1/separase, a cysteine endopeptidase, is a key player in centrosome duplication and mitotic sister chromatid separation. Aberrant expression and/or altered separase proteolytic activity are associated with centrosome amplification, aneuploidy, tumorigenesis and disease progression. Since centrosome alterations are a common and early detectable feature in patients with myelodysplastic syndrome (MDS) and cytogenetic aberrations play an important role in disease risk stratification, we examined separase activity on single cell level in 67 bone marrow samples obtained from patients with MDS, secondary acute myeloid leukemia (sAML), de novo acute myeloid leukemia (AML) and healthy controls by a flow cytometric separase activity assay...
2018: PloS One
https://www.readbyqxmd.com/read/29339437/spr2-protects-minus-ends-to-promote-severing-and-reorientation-of-plant-cortical-microtubule-arrays
#17
Masayoshi Nakamura, Jelmer J Lindeboom, Marco Saltini, Bela M Mulder, David W Ehrhardt
The cortical microtubule arrays of higher plants are organized without centrosomes and feature treadmilling polymers that are dynamic at both ends. The control of polymer end stability is fundamental for the assembly and organization of cytoskeletal arrays, yet relatively little is understood about how microtubule minus ends are controlled in acentrosomal microtubule arrays, and no factors have been identified that act at the treadmilling minus ends in higher plants. Here, we identify Arabidopsis thaliana SPIRAL2 (SPR2) as a protein that tracks minus ends and protects them against subunit loss...
March 5, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29330283/centriole-overduplication-is-the-predominant-mechanism-leading-to-centrosome-amplification-in-melanoma
#18
Ryan A Denu, Maria Shabbir, Minakshi Nihal, Chandra K Singh, B Jack Longley, Mark E Burkard, Nihal Ahmad
Centrosome amplification (CA) is common in cancer and can arise by centriole overduplication or by cell doubling events, including the failure of cell division and cell-cell fusion. To assess the relative contributions of these two mechanisms, the number of centrosomes with mature/mother centrioles was examined by immunofluorescence in a tissue microarray of human melanomas and benign nevi ( n = 79 and 17, respectively). The centrosomal protein 170 (CEP170) was used to identify centrosomes with mature centrioles; this is expected to be present in most centrosomes with cell doubling, but on fewer centrosomes with overduplication...
March 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29307730/zyg-1-promotes-limited-centriole-amplification-in-the-c-elegans-seam-lineage
#19
Benita Wolf, Fernando R Balestra, Antoine Spahr, Pierre Gönczy
Genome stability relies notably on the integrity of centrosomes and on the mitotic spindle they organize. Structural and numerical centrosome aberrations are frequently observed in human cancer, and there is increasing evidence that centrosome amplification can promote tumorigenesis. Here, we use C. elegans seam cells as a model system to analyze centrosome homeostasis in the context of a stereotyped stem like lineage. We found that overexpression of the Plk4-related kinase ZYG-1 leads to the formation of one supernumerary centriolar focus per parental centriole during the cell cycle that leads to the sole symmetric division in the seam lineage...
February 15, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29243212/controlling-centriole-numbers-geminin-family-members-as-master-regulators-of-centriole-amplification-and-multiciliogenesis
#20
REVIEW
Marina Arbi, Dafni-Eleftheria Pefani, Stavros Taraviras, Zoi Lygerou
To ensure that the genetic material is accurately passed down to daughter cells during mitosis, dividing cells must duplicate their chromosomes and centrosomes once and only once per cell cycle. The same key steps-licensing, duplication, and segregation-control both the chromosome and the centrosome cycle, which must occur in concert to safeguard genome integrity. Aberrations in genome content or centrosome numbers lead to genomic instability and are linked to tumorigenesis. Such aberrations, however, can also be part of the normal life cycle of specific cell types...
December 14, 2017: Chromosoma
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