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https://www.readbyqxmd.com/read/29276125/nek9-phosphorylation-defines-a-new-role-for-tpx2-in-eg5-dependent-centrosome-separation-before-nuclear-envelope-breakdown
#1
Susana Eibes, Núria Gallisà-Suñé, Miquel Rosas-Salvans, Paula Martínez-Delgado, Isabelle Vernos, Joan Roig
Centrosomes [1, 2] play a central role during spindle assembly in most animal cells [3]. In early mitosis, they organize two symmetrical microtubule arrays that upon separation define the two poles of the forming spindle. Centrosome separation is tightly regulated [4, 5], occurring through partially redundant mechanisms that rely on the action of microtubule-based dynein and kinesin motors and the actomyosin system [6]. While centrosomes can separate in prophase or in prometaphase after nuclear envelope breakdown (NEBD), prophase centrosome separation optimizes spindle assembly and minimizes the occurrence of abnormal chromosome attachments that could end in aneuploidy [7, 8]...
December 13, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29233929/single-cell-rna-seq-reveals-a-subpopulation-of-prostate-cancer-cells-with-enhanced-cell-cycle-related-transcription-and-attenuated-androgen-response
#2
Aaron M Horning, Yao Wang, Che-Kuang Lin, Anna D Louie, Rohit R Jadhav, Chia-Nung Hung, Chiou-Miin Wang, Chun-Lin Lin, Nameer B Kirma, Michael A Liss, Addanki P Kumar, LuZhe Sun, Zhijie Liu, Wei-Ting Chao, Qianben Wang, Victor X Jin, Chun-Liang Chen, Tim H-M Huang
Increasing evidence suggests the presence of minor cell subpopulations in prostate cancer that are androgen independent and poised for selection as dominant clones after androgen-deprivation therapy. In this study, we investigated this phenomenon by stratifying cell subpopulations based on transcriptome profiling of 144 single LNCaP prostate cancer cells treated or untreated with androgen after cell cycle synchronization. Model-based clustering of 397 differentially expressed genes identified eight potential subpopulations of LNCaP cells, revealing a previously unappreciable level of cellular heterogeneity to androgen stimulation...
December 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/29156688/frequency-of-expression-and-generation-of-t-cell-responses-against-antigens-on-multiple-myeloma-cells-in-patients-included-in-the-gmmg-mm5-trial
#3
Michael Schmitt, Angela G Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
Background: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. Results: Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152086/cox-2-seh-dual-inhibitor-ptupb-suppresses-glioblastoma-growth-by-targeting-epidermal-growth-factor-receptor-and-hyaluronan-mediated-motility-receptor
#4
Junyang Li, Yali Zhou, Handong Wang, Yongyue Gao, Liwen Li, Sung Hee Hwang, Xiangjun Ji, Bruce D Hammock
Aims: Cyclooxygenase-2 (COX-2)/soluble epoxide hydrolase (sEH) dual inhibitor, PTUPB, has been demonstrated to inhibit angiogenesis, primary tumor growth and metastasis. The aim of this study is to investigate the effects of PTUPB on glioblastoma cells and xenograft model. Results: We show here that PTUPB inhibits glioblastoma cell proliferation and G1 phase cell cycle arrest in vitro, and suppresses the tumor growth and angiogenesis in vivo. The expression and activation of epidermal growth factor receptor (EGFR) and its downstream kinases, ERK1/2 and AKT, are reduced by PTUPB, indicating that the EGF/EGFR signaling pathway is a potential target...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28994651/hmmr-acts-in-the-plk1-dependent-spindle-positioning-pathway-and-supports-neural-development
#5
Marisa Connell, Helen Chen, Jihong Jiang, Chia-Wei Kuan, Abbas Fotovati, Tony Lh Chu, Zhengcheng He, Tess C Lengyell, Huaibiao Li, Torsten Kroll, Amanda M Li, Daniel Goldowitz, Lucien Frappart, Aspasia Ploubidou, Millan S Patel, Linda M Pilarski, Elizabeth M Simpson, Philipp F Lange, Douglas W Allan, Christopher A Maxwell
Oriented cell division is one mechanism progenitor cells use during development and to maintain tissue homeostasis. Common to most cell types is the asymmetric establishment and regulation of cortical NuMA-dynein complexes that position the mitotic spindle. Here, we discover that HMMR acts at centrosomes in a PLK1-dependent pathway that locates active Ran and modulates the cortical localization of NuMA-dynein complexes to correct mispositioned spindles. This pathway was discovered through the creation and analysis of Hmmr-knockout mice, which suffer neonatal lethality with defective neural development and pleiotropic phenotypes in multiple tissues...
October 10, 2017: ELife
https://www.readbyqxmd.com/read/28993511/cell-cycle-dependent-tumor-engraftment-and-migration-are-enabled-by-aurora-a
#6
Tony L H Chu, Marisa Connell, Lixin Zhou, Zhengcheng He, Jennifer R Won, Seyed M Rahavi, Helen Chen, Pooja Mohan, Oksana Nemirovsky, Abbas Fotovati, Miguel Angel Pujana, Gregor Sd Reid, Torsten O Nielsen, Nelly Pante, Christopher A Maxwell
Cell cycle progression and the acquisition of a migratory phenotype are hallmarks of human carcinoma cells that are perceived as independent processes but may be interconnected by molecular pathways that control microtubule nucleation at centrosomes. Here, cell cycle progression dramatically impacts the engraftment kinetics of 4T1-luciferase2 breast cancer cells in immunocompetent BALB/c or immunocompromised NOD-SCID gamma (NSG) mice. Multi-parameter imaging of wound closure assays was used to track cell cycle progression, cell migration, and associated phenotypes in epithelial cells or carcinoma cells expressing a fluorescence ubiquitin cell cycle indicator...
October 9, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28595038/bio-electric-field-enhancement-the-influence-on-hyaluronan-mediated-motility-receptors-in-human-breast-carcinoma
#7
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/28591191/reanalysis-of-brca1-2-negative-high-risk-ovarian-cancer-patients-reveals-novel-germline-risk-loci-and-insights-into-missing-heritability
#8
Jaime L Stafford, Gregory Dyson, Nancy K Levin, Sophia Chaudhry, Rita Rosati, Hasini Kalpage, Courtney Wernette, Nancie Petrucelli, Michael S Simon, Michael A Tainsky
While up to 25% of ovarian cancer (OVCA) cases are thought to be due to inherited factors, the majority of genetic risk remains unexplained. To address this gap, we sought to identify previously undescribed OVCA risk variants through the whole exome sequencing (WES) and candidate gene analysis of 48 women with ovarian cancer and selected for high risk of genetic inheritance, yet negative for any known pathogenic variants in either BRCA1 or BRCA2. In silico SNP analysis was employed to identify suspect variants followed by validation using Sanger DNA sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/28427147/brca1-controls-the-cell-division-axis-and-governs-ploidy-and-phenotype-in-human-mammary-cells
#9
Zhengcheng He, Nagarajan Kannan, Oksana Nemirovsky, Helen Chen, Marisa Connell, Brian Taylor, Jihong Jiang, Linda M Pilarski, Markus C Fleisch, Dieter Niederacher, Miguel Angel Pujana, Connie J Eaves, Christopher A Maxwell
BRCA1 deficiency may perturb the differentiation hierarchy present in the normal mammary gland and is associated with the genesis of breast cancers that are genomically unstable and typically display a basal-like transcriptome. Oriented cell division is a mechanism known to regulate cell fates and to restrict tumor formation. We now show that the cell division axis is altered following shRNA-mediated BRCA1 depletion in immortalized but non-tumorigenic, or freshly isolated normal human mammary cells with graded consequences in progeny cells that include aneuploidy, perturbation of cell polarity in spheroid cultures, and a selective loss of cells with luminal features...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28217782/receptor-for-hyaluronan-mediated-motility-rhamm-hmmr-is-a-novel-target-for-promoting-subcutaneous-adipogenesis
#10
S B Bahrami, C Tolg, T Peart, C Symonette, M Veiseh, J U Umoh, D W Holdsworth, J B McCarthy, L G Luyt, M J Bissell, A Yazdani, E A Turley
Hyaluronan, CD44 and the Receptor for Hyaluronan-Mediated Motility (RHAMM, gene name HMMR) regulate stem cell differentiation including mesenchymal progenitor differentiation. Here, we show that CD44 expression is required for subcutaneous adipogenesis, whereas RHAMM expression suppresses this process. We designed RHAMM function blocking peptides to promote subcutaneous adipogenesis as a clinical and tissue engineering tool. Adipogenic RHAMM peptides were identified by screening for their ability to promote adipogenesis in culture assays using rat bone marrow mesenchymal stem cells, mouse pre-adipocyte cell lines and primary human subcutaneous pre-adipocytes...
March 1, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28196904/extracellular-matrix-receptor-expression-in-subtypes-of-lung-adenocarcinoma-potentiates-outgrowth-of-micrometastases
#11
Laura E Stevens, William K C Cheung, Sally J Adua, Anna Arnal-Estapé, Minghui Zhao, Zongzhi Liu, Kelly Brewer, Roy S Herbst, Don X Nguyen
Mechanisms underlying the propensity of latent lung adenocarcinoma (LUAD) to relapse are poorly understood. In this study, we show how differential expression of a network of extracellular matrix (ECM) molecules and their interacting proteins contributes to risk of relapse in distinct LUAD subtypes. Overexpression of the hyaluronan receptor HMMR in primary LUAD was associated with an inflammatory molecular signature and poor prognosis. Attenuating HMMR in LUAD cells diminished their ability to initiate lung tumors and distant metastases...
April 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/27932211/a-novel-class-of-somatic-mutations-in-blood-detected-preferentially-in-cd8-cells
#12
Miko Valori, Lilja Jansson, Anna Kiviharju, Pekka Ellonen, Hanna Rajala, Shady Adnan Awad, Satu Mustjoki, Pentti J Tienari
Somatic mutations have a central role in cancer but their role in other diseases such as autoimmune disorders is poorly understood. Earlier work has provided indirect evidence of rare somatic mutations in autoreactive T-lymphocytes in multiple sclerosis (MS) patients but such mutations have not been identified thus far. We analysed somatic mutations in blood in 16 patients with relapsing MS and 4 with other neurological autoimmune disease. To facilitate the detection of somatic mutations CD4+, CD8+, CD19+ and CD4-/CD8-/CD19- cell subpopulations were separated...
February 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27920576/hmmr-antisense-rna-1-a-novel-long-noncoding-rna-regulates-the-progression-of-basal-like-breast-cancer-cells
#13
Wei Liu, Jun Ma, Yong Cheng, Hongbo Zhang, Wengguang Luo, Hongyan Zhang
Recently, accumulating evidence has suggested that long noncoding RNAs (lncRNAs) play crucial roles in carcinogenesis and cancer progression. Hyaluronan-mediated motility receptor (HMMR) is an essential cancer-related gene in basal-like breast cancer (BLBC). In our study, HMMR antisense RNA 1 (HMMR-AS1) was analyzed in BLBC patients through polymerase chain reaction analysis. Here, we found that the expression of HMMR was positively correlated with HMMR-AS1 (RP11-80G.1). When HMMR-AS1 (RP11-80G.1) was knocked down, the expression of HMMR markedly reduced...
2016: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/27659531/the-tumor-associated-antigen-rhamm-hmmr-cd168-is-expressed-by-monocyte-derived-dendritic-cells-and-presented-to-t-cells
#14
Yannick Willemen, Johan M J Van den Bergh, Sarah M Bonte, Sébastien Anguille, Carlo Heirman, Barbara M H Stein, Herman Goossens, Tessa Kerre, Kris Thielemans, Marc Peeters, Viggo F I Van Tendeloo, Evelien L J Smits, Zwi N Berneman
We formerly demonstrated that vaccination with Wilms' tumor 1 (WT1)-loaded autologous monocyte-derived dendritic cells (mo-DCs) can be a well-tolerated effective treatment in acute myeloid leukemia (AML) patients. Here, we investigated whether we could introduce the receptor for hyaluronic acid-mediated motility (RHAMM/HMMR/CD168), another clinically relevant tumor-associated antigen, into these mo-DCs through mRNA electroporation and elicit RHAMM-specific immune responses. While RHAMM mRNA electroporation significantly increased RHAMM protein expression by mo-DCs, our data indicate that classical mo-DCs already express and present RHAMM at sufficient levels to activate RHAMM-specific T cells, regardless of electroporation...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27533084/frequency-of-expression-and-generation-of-t-cell-responses-against-antigens-on-multiple-myeloma-cells-in-patients-included-in-the-gmmg-mm5-trial
#15
Michael Schmitt, Angela G Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
BACKGROUND: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. RESULTS: Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing...
August 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/26459475/effects-of-rhamm-hmmr-selective-peptides-on-survival-of-breast-cancer-cells
#16
N P Akent'eva, S S Shushanov, A I Kotel'nikov
RHAMM-selective peptides in a concentration of 10 μg/ml (2×10(-7) M) inhibited the growth of MDA-MB-231 breast cancer cells over 48 h. Treatment of cancer cells with RHAMM-selective peptides induced apoptosis and necrosis and increased caspase-3 activity (by 30%).
September 2015: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/26456171/identification-design-and-synthesis-of-tubulin-derived-peptides-as-novel-hyaluronan-mimetic-ligands-for-the-receptor-for-hyaluronan-mediated-motility-rhamm-hmmr
#17
Kenneth Virgel N Esguerra, Cornelia Tolg, Natalia Akentieva, Matthew Price, Choi-Fong Cho, John D Lewis, James B McCarthy, Eva A Turley, Leonard G Luyt
Fragments of the extracellular matrix component hyaluronan (HA) promote tissue inflammation, fibrosis and tumor progression. HA fragments act through HA receptors including CD44, LYVE1, TLR2, 4 and the receptor for hyaluronan mediated motility (RHAMM/HMMR). RHAMM is a multifunctional protein with both intracellular and extracellular roles in cell motility and proliferation. Extracellular RHAMM binds directly to HA fragments while intracellular RHAMM binds directly to ERK1 and tubulin. Both HA and regions of tubulin (s-tubulin) are anionic and bind to basic amino acid-rich regions in partner proteins, such as in HA and tubulin binding regions of RHAMM...
December 2015: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/26439031/identification-of-potential-therapeutic-target-genes-and-mechanisms-in-non-small-cell-lung-carcinoma-in-non-smoking-women-based-on-bioinformatics-analysis
#18
W Zhou, M Yin, H Cui, N Wang, L-L Zhao, L-Z Yuan, X-P Yang, X-M Ding, F-Z Men, X Ma, J-R Na
OBJECTIVE: The study was aimed to explore the underlying mechanisms and identify the potential target genes by bioinformatics analysis for non-small-cell lung carcinoma (NSCLC) treatment in non-smoking women. MATERIALS AND METHODS: The microarray data of GSE19804 was downloaded from Gene Expression Omnibus (GEO) database. Paired samples (from the same patient) of tumor and normal lung tissues from 60 non-smoking female NSCLC patients were used to identify differentially expressed genes (DEGs)...
September 2015: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/26295306/combined-expressional-analysis-bioinformatics-and-targeted-proteomics-identify-new-potential-therapeutic-targets-in-glioblastoma-stem-cells
#19
COMPARATIVE STUDY
Biljana Stangeland, Awais A Mughal, Zanina Grieg, Cecilie Jonsgar Sandberg, Mrinal Joel, Ståle Nygård, Torstein Meling, Wayne Murrell, Einar O Vik Mo, Iver A Langmoen
Glioblastoma (GBM) is both the most common and the most lethal primary brain tumor. It is thought that GBM stem cells (GSCs) are critically important in resistance to therapy. Therefore, there is a strong rationale to target these cells in order to develop new molecular therapies.To identify molecular targets in GSCs, we compared gene expression in GSCs to that in neural stem cells (NSCs) from the adult human brain, using microarrays. Bioinformatic filtering identified 20 genes (PBK/TOPK, CENPA, KIF15, DEPDC1, CDC6, DLG7/DLGAP5/HURP, KIF18A, EZH2, HMMR/RHAMM/CD168, NOL4, MPP6, MDM1, RAPGEF4, RHBDD1, FNDC3B, FILIP1L, MCC, ATXN7L4/ATXN7L1, P2RY5/LPAR6 and FAM118A) that were consistently expressed in GSC cultures and consistently not expressed in NSC cultures...
September 22, 2015: Oncotarget
https://www.readbyqxmd.com/read/26156497/extracellular-component-hyaluronic-acid-and-its-receptor-hmmr-are-required-for-epicardial-emt-during-heart-regeneration
#20
Maria A Missinato, Kimimasa Tobita, Nicla Romano, James A Carroll, Michael Tsang
AIMS: After injury, the adult zebrafish can regenerate the heart. This requires the activation of the endocardium and epicardium as well as the proliferation of pre-existing cardiomyocytes to replace the lost tissue. However, the molecular mechanisms involved in this process are not completely resolved. In this work, we aim to identify the proteins involved in zebrafish heart regeneration and to explore their function. METHODS AND RESULTS: Using a proteomic approach, we identified Hyaluronan-mediated motility receptor (Hmmr), a hyaluronic acid (HA) receptor, to be expressed following ventricular resection in zebrafish...
September 1, 2015: Cardiovascular Research
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