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https://www.readbyqxmd.com/read/28649649/patterns-of-cell-cycle-checkpoint-deregulation-associated-with-intrinsic-molecular-subtypes-of-human-breast-cancer-cells
#1
Jacquelyn J Bower, Leah D Vance, Matthew Psioda, Stephanie L Smith-Roe, Dennis A Simpson, Joseph G Ibrahim, Katherine A Hoadley, Charles M Perou, William K Kaufmann
Genomic instability is a hallmark of breast cancer, contributes to tumor heterogeneity, and influences chemotherapy resistance. Although Gap 2 and mitotic checkpoints are thought to prevent genomic instability, the role of these checkpoints in breast cancer is poorly understood. Here, we assess the Gap 2 and mitotic checkpoint functions of 24 breast cancer and immortalized mammary epithelial cell lines representing four of the six intrinsic molecular subtypes of breast cancer. We found that patterns of cell cycle checkpoint deregulation were associated with the intrinsic molecular subtype of breast cancer cell lines...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28649434/a-clb-cdk1-mediated-regulation-of-fkh2-synchronizes-clb-expression-in-the-budding-yeast-cell-cycle
#2
Christian Linke, Anastasia Chasapi, Alberto González-Novo, Istabrak Al Sawad, Silvia Tognetti, Edda Klipp, Mart Loog, Sylvia Krobitsch, Francesc Posas, Ioannis Xenarios, Matteo Barberis
Precise timing of cell division is achieved by coupling waves of cyclin-dependent kinase (Cdk) activity with a transcriptional oscillator throughout cell cycle progression. Although details of transcription of cyclin genes are known, it is unclear which is the transcriptional cascade that modulates their expression in a timely fashion. Here, we demonstrate that a Clb/Cdk1-mediated regulation of the Fkh2 transcription factor synchronizes the temporal mitotic CLB expression in budding yeast. A simplified kinetic model of the cyclin/Cdk network predicts a linear cascade where a Clb/Cdk1-mediated regulation of an activator molecule drives CLB3 and CLB2 expression...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28648284/common-molecular-subtypes-among-asian-hepatocellular-carcinoma-and-cholangiocarcinoma
#3
Jittiporn Chaisaingmongkol, Anuradha Budhu, Hien Dang, Siritida Rabibhadana, Benjarath Pupacdi, So Mee Kwon, Marshonna Forgues, Yotsawat Pomyen, Vajarabhongsa Bhudhisawasdi, Nirush Lertprasertsuke, Anon Chotirosniramit, Chawalit Pairojkul, Chirayu U Auewarakul, Thaniya Sricharunrat, Kannika Phornphutkul, Suleeporn Sangrajrang, Maggie Cam, Ping He, Stephen M Hewitt, Kris Ylaya, Xiaolin Wu, Jesper B Andersen, Snorri S Thorgeirsson, Joshua J Waterfall, Yuelin J Zhu, Jennifer Walling, Holly S Stevenson, Daniel Edelman, Paul S Meltzer, Christopher A Loffredo, Natsuko Hama, Tatsuhiro Shibata, Robert H Wiltrout, Curtis C Harris, Chulabhorn Mahidol, Mathuros Ruchirawat, Xin W Wang
Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are clinically disparate primary liver cancers with etiological and biological heterogeneity. We identified common molecular subtypes linked to similar prognosis among 199 Thai ICC and HCC patients through systems integration of genomics, transcriptomics, and metabolomics. While ICC and HCC share recurrently mutated genes, including TP53, ARID1A, and ARID2, mitotic checkpoint anomalies distinguish the C1 subtype with key drivers PLK1 and ECT2, whereas the C2 subtype is linked to obesity, T cell infiltration, and bile acid metabolism...
June 6, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28646352/lead-enhancement-of-3t3-l1-fibroblasts-differentiation-to-adipocytes-involves-erk-c-ebp%C3%AE-and-ppar%C3%AE-activation
#4
Claudia Noemí Martini, Matías Gabrielli, Graciela Bonifacino, María Magdalena Codesido, María Del Carmen Vila
Lead (Pb) is an environmental and industrial contaminant that still represents a public health problem. Elevated Pb exposure has been inversely correlated with femoral bone density and associated with osteoporosis. In the last years, it has been shown that inhibition of osteogenesis from mesenchymal stem cells activates adipogenesis and vice versa. In this paper, we investigated the effect of Pb on the differentiation of 3T3-L1 fibroblasts to adipocytes which is the cell model most used to study adipogenesis...
June 23, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28645917/multivalent-binding-of-pwwp2a-to-h2a-z-regulates-mitosis-and-neural-crest-differentiation
#5
Sebastian Pünzeler, Stephanie Link, Gabriele Wagner, Eva C Keilhauer, Nina Kronbeck, Ramona Mm Spitzer, Susanne Leidescher, Yolanda Markaki, Edith Mentele, Catherine Regnard, Katrin Schneider, Daisuke Takahashi, Masayuki Kusakabe, Chiara Vardabasso, Lisa M Zink, Tobias Straub, Emily Bernstein, Masahiko Harata, Heinrich Leonhardt, Matthias Mann, Ralph Aw Rupp, Sandra B Hake
Replacement of canonical histones with specialized histone variants promotes altering of chromatin structure and function. The essential histone variant H2A.Z affects various DNA-based processes via poorly understood mechanisms. Here, we determine the comprehensive interactome of H2A.Z and identify PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A is a functionally uncharacterized, vertebrate-specific protein that binds very tightly to chromatin through a concerted multivalent binding mode. Two internal protein regions mediate H2A...
June 23, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28645196/antagonistic-regulation-of-cyclin-expression-by-the-bzip-transcription-factors-pcr1-and-atf1-during-g2-m-transition
#6
Sushobhana Bandyopadhyay, Protiti Maiti Ghosh, Sohini Basu, Madhurima Paul, Syed Benazir Alam, Elizabeth Das, Geetanjali Sundaram
The transcription factor Atf1 is known to promote cell survival during various stress conditions in Schizosaccharomyces pombe by activating the expression of appropriate genes. It can also activate transcription of other important genes responsible for cell cycle progression. An Atf1 dependent increase in the expression of cell division promoting genes will oppose activation of checkpoints necessary to ensure repairs and cell survival during stress. Hence selective inhibition of the cell cycle related functions of Atf1 would be indispensable for cellular survival during stress...
June 22, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28638452/targeting-tpx2-suppresses-the-tumorigenesis-of-hepatocellular-carcinoma-cells-resulting-in-arrested-mitotic-phase-progression-and-increased-genomic-instability
#7
Chao-Wen Hsu, Yu-Chia Chen, Hsing-Hao Su, Guan-Jin Huang, Chih-Wen Shu, Tony Tong-Lin Wu, Hung-Wei Pan
Hepatocellular carcinoma (HCC) remains one of the most difficult cancers to treat, with chemotherapies being relatively ineffective. Therefore, a better knowledge of molecular hepatocarcinogenesis will provide opportunities for designing targeted therapies. TPX2 (targeting protein for Xklp2) is overexpressed as a consequence of oncogenic alterations and is likely to alter the proper regulation of chromosome segregation in cancer cells. Disrupting the machinery which is responsible for mitosis and chromosome instability in cancer cells can be one of the most successful strategies for cancer therapy...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28634860/molecular-chaperone-hsp70-and-its-constitutively-active-form-hsc70-play-an-indispensable-role-during-eye-development-of-drosophila-melanogaster
#8
Ajay Kumar, Anand K Tiwari
In the present study, we demonstrate that molecular chaperone Hsp70 and Hsc70 is essential for normal organization and development of ommatidial cells in Drosophila melanogaster eye. An exogenously expressed dominant negative mutant of Hsp70 (K71E) and Hsc70.4 (K71S and D206S) in an eye-specific manner resulted in eye degeneration that includes loss of eye pigment, disorganized ommatidia, abnormality in bristle cell arrangement and reduction in the eye size. The developmental organization of ommatidial cells (cone, photoreceptor, pigment, and bristle cell complex) was disturbed in Hsp70 and Hsc70 mutants...
June 20, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28634159/a-role-for-the-nonsense-mediated-mrna-decay-pathway-in-maintaining-genome-stability-in-caenorhabditis-elegans
#9
Víctor González-Huici, Bin Wang, Anton Gartner
Ionizing radiation (IR) is commonly used in cancer therapy and is a main source of DNA double-strand-breaks (DSBs), one of the most toxic forms of DNA damage. We have used Caenorhabditis elegans as an invertebrate model to identify novel factors required for repair of DNA damage inflicted by IR. We have performed an unbiased genetic screen, finding that smg-1 mutations confer strong hypersensitivity to IR. SMG-1 is a phosphoinositide-3 kinase (PI3K) kinase involved in mediating nonsense-mediated mRNA decay (NMD) of transcripts containing premature stop codons and related to the ATM and ATR kinases which are at the apex of DNA damage signalling pathways...
June 20, 2017: Genetics
https://www.readbyqxmd.com/read/28633016/mll-wdr5-complex-regulates-kif2a-localization-to-ensure-chromosome-congression-and-proper-spindle-assembly-during-mitosis
#10
Aamir Ali, Sailaja Naga Veeranki, Akash Chinchole, Shweta Tyagi
Mixed-lineage leukemia (MLL), along with multisubunit (WDR5, RbBP5, ASH2L, and DPY30) complex catalyzes the trimethylation of H3K4, leading to gene activation. Here, we characterize a chromatin-independent role for MLL during mitosis. MLL and WDR5 localize to the mitotic spindle apparatus, and loss of function of MLL complex by RNAi results in defects in chromosome congression and compromised spindle formation. We report interaction of MLL complex with several kinesin and dynein motors. We further show that the MLL complex associates with Kif2A, a member of the Kinesin-13 family of microtubule depolymerase, and regulates the spindle localization of Kif2A during mitosis...
June 19, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28630940/fluconazole-induced-ploidy-change-in-cryptococcus-neoformans-results-from-the-uncoupling-of-cell-growth-and-nuclear-division
#11
Sophie Altamirano, Diana Fang, Charles Simmons, Shreyas Sridhar, Peipei Wu, Kaustuv Sanyal, Lukasz Kozubowski
Cryptococcus neoformans is a pathogenic yeast that causes lethal cryptococcal meningitis in immunocompromised patients. One of the challenges in treating cryptococcosis is the development of resistance to azole antifungals. Previous studies linked azole resistance to elevated numbers of copies of critical resistance genes in aneuploid cells. However, how aneuploidy is formed in the presence of azole drugs remains unclear. This study showed that treatment with inhibitory concentrations of an azole drug, fluconazole (FLC), resulted in a significant population of cells with increased DNA content, through the following defects: inhibition of budding, premature mitosis, and inhibition of cytokinesis followed by replication in the mother cell...
May 2017: MSphere
https://www.readbyqxmd.com/read/28625535/glial-specific-functions-of-microcephaly-protein-wdr62-and-interaction-with-the-mitotic-kinase-aurka-are-essential-for-drosophila-brain-growth
#12
Nicholas R Lim, Belal Shohayeb, Olga Zaytseva, Naomi Mitchell, S Sean Millard, Dominic C H Ng, Leonie M Quinn
The second most commonly mutated gene in primary microcephaly (MCPH) patients is wd40-repeat protein 62 (wdr62), but the relative contribution of WDR62 function to the growth of major brain lineages is unknown. Here, we use Drosophila models to dissect lineage-specific WDR62 function(s). Interestingly, although neural stem cell (neuroblast)-specific depletion of WDR62 significantly decreased neuroblast number, brain size was unchanged. In contrast, glial lineage-specific WDR62 depletion significantly decreased brain volume...
June 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28622294/hepatocyte-nuclear-factor-1b-is-a-novel-negative-regulator-of-white-adipocyte-differentiation
#13
Xin Wang, Hao Wu, Weihua Yu, Jiangzheng Liu, Jie Peng, Nai Liao, Jieling Zhang, Xiaodi Zhang, Chunxu Hai
Hepatocyte nuclear factor 1b (HNF1b) is a transcription factor belonging to the HNF family. We aimed to investigate the role of HNF1b in white adipocyte differentiation. The expression of HNF1b was reduced in white adipose tissue (WAT) of both diet-induced and genetic obese mice and decreased during the process of 3T3-L1 adipocyte differentiation. Downregulation of HNF1b enhanced 3T3-L1 adipocyte differentiation and upregulation of HNF1b inhibited this process. Upregulation of HNF1b inhibited peroxisome proliferator-activated receptor γ (PPARγ) and its target gene expression, while downregulation of HNF1b increased those genes expression...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28619818/antagonistic-regulation-of-the-second-mitotic-wave-by-eyes-absent-sine-oculis-and-combgap-coordinates-proliferation-and-specification-in-the-drosophila-retina
#14
Trevor L Davis, Ilaria Rebay
The transition from proliferation to specification is fundamental to the development of appropriately patterned tissues. In the developing Drosophila eye, Eyes absent (Eya) and Sine oculis (So) orchestrate the progression of progenitor cells from asynchronous cell division to G1 arrest and neuronal specification at the morphogenetic furrow. Here, we uncover a novel role for Eya and So in promoting cell cycle exit in the Second Mitotic Wave (SMW), a synchronized, terminal cell division that occurs several hours after passage of the furrow...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28612617/-breast-cancer-in-young-women-correlation-of-clinical-histomorphological-and-molecular-genetic-features-of-breast-carcinoma-in-women-younger-than-35-years-of-age
#15
A Metelková, A Skálová, J Fínek
BACKGROUND: Worldwide, breast cancer is the leading type of malignancy in women. For premenopausal women, the disease brings much higher risk as it is usually more aggressive with worse prognosis. PATIENTS AND METHODS: In this retrospective study, 92 women treated at the Department of Oncology and Radiotherapy in Pilsen were selected from a basic cohort of 356 women under 35 years of age with breast cancer who were diagnosed between 2006 and 2015. The control group comprised 100 postmenopausal women over 65 years of age who were treated for invasive breast cancer...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28606862/pathogenicity-profile-of-vibrio-parahaemolyticus-in-farmed-pacific-white-shrimp-penaeus-vannamei
#16
R Ananda Raja, R Sridhar, C Balachandran, A Palanisammi, S Ramesh, K Nagarajan
A pathobiological study was conducted using Vibrio parahaemolyticus (VP) strain isolated from vibriosis affected shrimp (Penaeus vannamei) farms in Kancheepuram and Thiruvallur districts of Tamil Nadu during August 2014 to February 2015. The isolate was identified based on the morphological, physiological, biochemical and molecular characters. LD50 value with intramuscular injection was determined as 2.6 × 10(4) cfu/shrimp and sequential pathology was studied giving 6.1 × 10(3) cfu/shrimp (LD25). Total plate count (TPC) and total Vibrio count (TVC) in water, pond sediment, haemolymph, muscle, HP and gut were found significantly (P < 0...
June 9, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28599653/dynamics-of-transcriptional-re-programming-of-syncytial-nuclei-in-developing-muscles
#17
Laetitia Bataillé, Hadi Boukhatmi, Jean-Louis Frendo, Alain Vincent
BACKGROUND: A stereotyped array of body wall muscles enables precision and stereotypy of animal movements. In Drosophila, each syncytial muscle forms via fusion of one founder cell (FC) with multiple fusion competent myoblasts (FCMs). The specific morphology of each muscle, i.e. distinctive shape, orientation, size and skeletal attachment sites, reflects the specific combination of identity transcription factors (iTFs) expressed by its FC. Here, we addressed three questions: Are FCM nuclei naive? What is the selectivity and temporal sequence of transcriptional reprogramming of FCMs recruited into growing syncytium? Is transcription of generic myogenic and identity realisation genes coordinated during muscle differentiation? RESULTS: The tracking of nuclei in developing muscles shows that FCM nuclei are competent to be transcriptionally reprogrammed to a given muscle identity, post fusion...
June 9, 2017: BMC Biology
https://www.readbyqxmd.com/read/28596487/znf131-suppresses-centrosome-fragmentation-in-glioblastoma-stem-like-cells-through-regulation-of-haus5
#18
Yu Ding, Jacob A Herman, Chad M Toledo, Jackie M Lang, Philip Corrin, Emily J Girard, Ryan Basom, Jeffrey J Delrow, James M Olson, Patrick J Paddison
Zinc finger domain genes comprise ~3% of the human genome, yet many of their functions remain unknown. Here we investigated roles for the vertebrate-specific BTB domain zinc finger gene ZNF131 in the context of human brain tumors. We report that ZNF131 is broadly required for Glioblastoma stem-like cell (GSC) viability, but dispensable for neural progenitor cell (NPC) viability. Examination of gene expression changes after ZNF131 knockdown (kd) revealed that ZNF131 activity notably promotes expression of Joubert Syndrome ciliopathy genes, including KIF7, NPHP1, and TMEM237, as well as HAUS5, a component of Augmin/HAUS complex that facilitates microtubule nucleation along the mitotic spindle...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28595038/bio-electric-field-enhancement-the-influence-on-hyaluronan-mediated-motility-receptors-in-human-breast-carcinoma
#19
Marcy C Purnell
Mechanisms that regulate cancer cell metastasis are often intricately linked to mechanisms that control cell migration in wound repair. Hyaluronan Mediated Motility Receptor (HMMR) encodes a receptor for hyaluronan-mediated motility (RHAMM), a non-integral cell surface hyaluronan receptor and intracellular protein that promotes mitotic spindle formation and cell motility. RHAMM has been found to have increased expression in both cancers and wounds, and when cancers show increased RHAMM expression poor outcomes have occurred...
April 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28592235/gene-centromere-mapping-in-meiotic-gynogenetic-european-seabass
#20
Münevver Oral, Julie Colléter, Michaël Bekaert, John B Taggart, Christos Palaiokostas, Brendan J McAndrew, Marc Vandeputte, Béatrice Chatain, Heiner Kuhl, Richard Reinhardt, Stefano Peruzzi, David J Penman
BACKGROUND: Fully isogenic lines in fish can be developed using "mitotic" gynogenesis (suppression of first zygotic mitosis following inactivation of the sperm genome). However, genome-wide verification of the steps in this process has seldom been applied. We used ddRADseq to generate SNP markers in a meiotic gynogenetic family of European seabass (Dicentrarchus labrax): (i) to verify the lack of paternal contribution in a meiotic gynogenetic family; (ii) to generate a gene-centromere map from this family; (iii) to identify telomeric markers that could distinguish mitotic gynogenetics from meiotic gynogenetics, which sometimes arise spontaneously in mitotic gynogenetic families...
June 7, 2017: BMC Genomics
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