scholarly journals NANOG/NANOGP8 Localizes at the Centrosome and is Spatiotemporally Associated with Centriole Maturation

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 692
Author(s):  
Erika Mikulenkova ◽  
Jakub Neradil ◽  
Ondrej Vymazal ◽  
Jan Skoda ◽  
Renata Veselska
Keyword(s):  
Tumor Cell ◽  
Nuclear Localization ◽  
Cell Types ◽  
Distal Region ◽  
Cell Fractionation ◽  
Tumor Cell Lines ◽  
Double Immunofluorescence ◽  
Transcriptional Regulatory ◽  
Mother Centriole

NANOG is a transcription factor involved in the regulation of pluripotency and stemness. The functional paralog of NANOG, NANOGP8, differs from NANOG in only three amino acids and exhibits similar reprogramming activity. Given the transcriptional regulatory role played by NANOG, the nuclear localization of NANOG/NANOGP8 has primarily been considered to date. In this study, we investigated the intriguing extranuclear localization of NANOG and demonstrated that a substantial pool of NANOG/NANOGP8 is localized at the centrosome. Using double immunofluorescence, the colocalization of NANOG protein with pericentrin was identified by two independent anti-NANOG antibodies among 11 tumor and non-tumor cell lines. The validity of these observations was confirmed by transient expression of GFP-tagged NANOG, which also colocalized with pericentrin. Mass spectrometry of the anti-NANOG immunoprecipitated samples verified the antibody specificity and revealed the expression of both NANOG and NANOGP8, which was further confirmed by real-time PCR. Using cell fractionation, we show that a considerable amount of NANOG protein is present in the cytoplasm of RD and NTERA-2 cells. Importantly, cytoplasmic NANOG was unevenly distributed at the centrosome pair during the cell cycle and colocalized with the distal region of the mother centriole, and its presence was markedly associated with centriole maturation. Along with the finding that the centrosomal localization of NANOG/NANOGP8 was detected in various tumor and non-tumor cell types, these results provide the first evidence suggesting a common centrosome-specific role of NANOG.

scholarly journals Expression of the MyoD1 muscle determination gene defines differentiation capability but not tumorigenicity of human rhabdomyosarcomas.

1989 ◽  
Vol 9 (11) ◽  
pp. 4722-4730 ◽  
Author(s):  
A L Hiti ◽  
E Bogenmann ◽  
F Gonzales ◽  
P A Jones
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Cell Types ◽  
Chain Gene ◽  
Tumor Cell Lines ◽  
Myosin Heavy Chain Gene ◽  
Mouse Muscle ◽  
Primary Explants ◽  
Rhabdomyosarcoma Cell ◽  
Multinucleated Myotubes

Several human rhabdomyosarcoma cell lines, cultured primary tumor explants, and biopsies of tumor and normal skeletal muscle tissue expressed a 2.0-kilobase transcript that hybridized to the mouse muscle determination gene MyoD1. This transcript was found in tumor cell lines and primary explants that developed multinucleated myotubes but was absent in Wilms' tumors or cell lines and primary explants that developed multinucleated myotubes but was absent in Wilms' tumors or cell lines derived from other mesenchymal tumor cell types. Expression of the human homolog of MyoD1 therefore can define a tumor as a rhabdomyosarcoma. Transfection of the mouse MyoD1 gene into the human rhabdomyosarcoma cell line RD increased the ability of the tumor cells to differentiate into multinucleated myotubes and enhanced myosin heavy-chain gene expression but did not decrease tumorigenicity in nude mice.

scholarly journals Cathepsin B activity in human lung tumor cell lines: ultrastructural localization, pH sensitivity, and inhibitor status at the cellular level.

1994 ◽  
Vol 42 (7) ◽  
pp. 917-929 ◽  
Author(s):  
E Spiess ◽  
A Brüning ◽  
S Gack ◽  
B Ulbricht ◽  
H Spring ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Tumor Cell ◽  
Enzymatic Activity ◽  
Cell Lines ◽  
Cathepsin B ◽  
Lung Tumor ◽  
Cell Types ◽  
Cellular Level ◽  
Tumor Cell Lines

We investigated the appearance and activity of the cysteine proteinase cathepsin B and its physiological inhibitors, stefins A and B, at the cellular level in human tumor cell lines HS-24, derived from a primary lung tumor (squamous cell), and SB-3, derived from a metastasis (lung adenocarcinoma). In addition to cathepsin B, these tumor cells also expressed the immunologically and functionally related cathepsin L, but not cathepsin H. Stefin A was found in HS-24 but not in SB-3 cells; stefin B was found in both cell types. Using a specific fluorogenic cytochemical assay, the intracellular activity of the enzyme was localized and quantified. Thus, the cellular cathepsin B kinetics for the synthetic substrates Z-Arg-Arg-4M beta NA and Z-Val-Lys-Lys-Arg-4M beta NA, its pH dependence and inhibition by E64, stefins A and B, and cystatin C could be determined. From these measurements it appeared that the enzyme exhibited different cleavage rates for these substrates in the different cell types, showed considerable cleavage activity at neutral pH, which was stable under these conditions for extended time periods, and was highly sensitive to the inhibitors E64 and cystatin C but was considerably less sensitive to stefins, particularly stefin A. By conventional light microscopy, confocal laser scanning microscopy, and electron microscopy the enzymatic activity was localized in lysosomes, as expected, but also in the endoplasmic reticulum, nuclear membrane, and plasma membrane. The endoplasmic reticulum is a site at which only pre-mature enzyme forms exist, which are usually not active. The appearance of enzymatic activity at the plasma membrane confirms earlier biochemical and immunofluorescence microscopic investigations. The different sites of localization within the cells make it likely that different forms of the enzyme are expressed simultaneously, which follow alternate ways of processing and sorting. Taken together, the results support an involvement of the enzyme under extracellular conditions in degradative processes.

Abstract B113: Role of I‐TAC‐binding receptors CXCR3 and CXCR7 in biology of various tumor cell lines

2009 ◽  
Author(s):  
Katarzyna Miekus ◽  
Danuta Jarocha ◽  
Elzbieta Trzyna ◽  
Marcin Majka
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Tumor Cell Lines

scholarly journals The ability to overcome multidrug resistance of tumor cell lines by novel acridine cytostatics with condensed heterocyclic rings.

2002 ◽  
Vol 49 (1) ◽  
pp. 87-92 ◽  
Author(s):  
Maria M Bontemps-Gracz ◽  
Agnieszka Kupiec ◽  
Ippolito Antonini ◽  
Edward Borowski
Keyword(s):  
Multidrug Resistance ◽  
Tumor Cell ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Human Tumor ◽  
Heterocyclic Ring ◽  
Tumor Cell Lines ◽  
Human Tumor Cell Lines

Two recently synthesized groups of acridine cytostatics containing fused heterocyclic ring(s): pyrazoloacridines (PAC) and pyrazolopyrimidoacridines (PPAC) were tested in regard to their in vitro cytotoxic activity towards a panel of sensitive and resistant human tumor cell lines. The obtained results corroborate our earlier hypothesis on the essential role of heterocyclic ring fused to the acridine moiety in the ability of acridine cytostatics to overcome multidrug resistance of tumor cells. The presence, location and kind of substituents considerably influenced both the cytotoxic activity of the derivatives and their ability to overcome multidrug resistance. The same factors also affected the cytostatics ability to differentiate between tumor cell lines with various types of drug exporting pumps.

scholarly journals Cancer Associated Fibroblast (CAF) regulation of PDAC parenchymal (CPC) and CSC phenotypes is modulated by ECM composition.

2020 ◽  
Author(s):  
Stefania Cannone ◽  
Maria Rafaella Greco ◽  
Hélène Guizouarn ◽  
Olivier Soriani ◽  
Richard Tomasini ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Fate ◽  
Survival Rates ◽  
Vasculogenic Mimicry ◽  
Cell Types ◽  
Collagen I ◽  
Ductal Adenocarcinoma ◽  
Metastatic Progression ◽  
Early Tumor

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest of all cancers having one of the lowest five-year survival rates. One of its hallmarks is a dense desmoplastic stroma consisting in the abnormal accumulation of extracellular matrix (ECM) components, especially Collagen I. This highly fibrotic stroma embeds the bulk cancer (parenchymal) cells (CPCs), cancer stem cells (CSCs) and the main producers of the stromal reaction, the Cancer Associated Fibroblasts (CAFs). Little is known about the role of the acellular ECM in the interplay of the CAFs with the different tumor cell types in determining their phenotypic plasticity and eventual cell fate. Methods Here, we analyzed the role of ECM collagen I in modulating the effect of CAF-derived signals by incubating PDAC CPCs and CSCs grown on ECM mimicking early (low collagen I levels) and late (high collagen I levels) stage PDAC stroma with conditioned medium from primary cultured CAFs derived from patients with PDAC in a previously described three-dimensional (3D) organotypic model of PDAC. Results We found that CAFs (1) reduced CPC growth while favoring CSC growth independently of the ECM; (2) increased the invasive capacity of only CPCs on the ECM mimicking the early tumor and (3) favored vasculogenic mimicry (VM) especially of the CSCs on the ECM mimicking an early tumor. Conclusions: We conclude that the CAFs and acellular stromal components interact to modulate the tumor behaviors of the PDAC CPC and CSC cell types and drive metastatic progression by stimulating the behavior of each tumor cell type that contribute to metastasis: invasion in the CPCs and growth and angiogenesis in the CSCs.

The Role of Mitochondrial Hexokinase Binding in the Abnormal Energy Metabolism of Tumor Cell Lines

1986 ◽  
Vol 488 (1 Membrane Path) ◽  
pp. 438-450 ◽  
Author(s):  
RICHARD A. NAKASHIMA ◽  
LAURA J. SCOTT ◽  
PETER L. PEDERSEN
Keyword(s):  
Energy Metabolism ◽  
Tumor Cell ◽  
Cell Lines ◽  
Tumor Cell Lines

PTEN and Autism With Macrocepaly

2013 ◽  
Author(s):  
Craig M. Powell
Keyword(s):  
Tumor Cell ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Clinical Phenotype ◽  
Model Systems ◽  
Tumor Cell Lines ◽  
Gene Encoding ◽  
Increased Risk ◽  
The Brain

Phosphatase and Tensin homolog deleted on chromosome 10 (PTEN) is a gene encoding an intracellular signaling molecule. PTEN was originally discovered as the gene responsible for a subset of familial hamartoma (tumor) syndromes associated with increased risk for certain cancers (Nelen et al., 1997) and as a gene often mutated in human cancers and tumor cell lines (Li et al., 1997; Steck et al., 1997). More recently, mutations in PTEN have been linked genetically to the clinical phenotype of autism or developmental delay with macrocephaly (Boccone et al., 2006; Butler et al., 2005; Buxbaum et al., 2007; Goffin, Hoefsloot, Bosgoed, Swillen, & Fryns, 2001; Herman, Butter, et al., 2007; McBride et al., 2010; Orrico et al., 2009; Stein, Elias, Saenz, Pickler, & Reynolds, 2010; Varga, Pastore, Prior, Herman, & McBride, 2009; Zori, Marsh, Graham, Marliss, & Eng, 1998). This chapter examines the role of PTEN in intracellular signaling, the link between PTEN signaling pathways and other autism-related genes and signaling pathways, the genetic relationship between PTEN and autism, model systems in which effects of Pten deletion on the brain have been studied, and promising preclinical data identifying therapeutic targets for patients with autism/macrocephaly associated with PTEN mutations.

Role of apoptosis and apoptosis-related proteins in the cisplatin-resistant phenotype of human tumor cell lines

APOPTOSIS ◽  
1997 ◽  
Vol 2 (6) ◽  
pp. 540-548 ◽  
Author(s):  
P. Perego ◽  
S. C. Righetti ◽  
R. Supino ◽  
D. Delia ◽  
C. Caserini ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Resistant Phenotype ◽  
Related Proteins

scholarly journals Inheritance of gene density–related higher order chromatin arrangements in normal and tumor cell nuclei

2003 ◽  
Vol 162 (5) ◽  
pp. 809-820 ◽  
Author(s):  
Marion Cremer ◽  
Katrin Küpper ◽  
Babett Wagler ◽  
Leah Wizelman ◽  
Johann v. Hase ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Radial Distribution ◽  
Normal Cell ◽  
Cell Types ◽  
Higher Order ◽  
Gene Density ◽  
Tumor Cell Lines ◽  
Cell Nuclei ◽  
Significant Difference

A gene density–related difference in the radial arrangement of chromosome territories (CTs) was previously described for human lymphocyte nuclei with gene-poor CT #18 located toward the nuclear periphery and gene-dense CT #19 in the nuclear interior (Croft, J.A., J.M. Bridger, S. Boyle, P. Perry, P. Teague, and W.A. Bickmore. 1999. J. Cell Biol. 145:1119–1131). Here, we analyzed the radial distribution of chromosome 18 and 19 chromatin in six normal cell types and in eight tumor cell lines, some of them with imbalances and rearrangements of the two chromosomes. Our findings demonstrate that a significant difference in the radial distribution of #18 and #19 chromatin is a common feature of higher order chromatin architecture in both normal and malignant cell types. However, in seven of eight tumor cell lines, the difference was less pronounced compared with normal cell nuclei due to a higher fraction of nuclei showing an inverted CT position, i.e., a CT #18 located more internally than a CT #19. This observation emphasizes a partial loss of radial chromatin order in tumor cell nuclei.

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