Cytoplasmic localization of the cell polarity factor scribble supports liver tumor formation and tumor cell invasiveness

Hepatology ◽  
2018 ◽  
Vol 67 (5) ◽  
pp. 1842-1856 ◽  
Author(s):  
Shan Wan ◽  
Anne-Sophie Meyer ◽  
Sofia Maria Elisabeth Weiler ◽  
Christian Rupp ◽  
Marcell Tóth ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Polarity ◽  
Liver Tumor ◽  
Tumor Formation ◽  
Cytoplasmic Localization ◽  
Cell Invasiveness ◽  
Polarity Factor

scholarly journals Regulation of CD44 Alternative Splicing by SRm160 and Its Potential Role in Tumor Cell Invasion

2006 ◽  
Vol 26 (1) ◽  
pp. 362-370 ◽  
Author(s):  
Chonghui Cheng ◽  
Phillip A. Sharp
Keyword(s):  
Alternative Splicing ◽  
Tumor Cell ◽  
Cell Invasion ◽  
Rna Splicing ◽  
Tumor Cell Invasion ◽  
Dependent Manner ◽  
Cd44 Isoforms ◽  
Transmembrane Glycoprotein ◽  
Cell Invasiveness ◽  
Interfering Rna

ABSTRACT The multiple isoforms of the transmembrane glycoprotein CD44 are produced by alternative RNA splicing. Expression of CD44 isoforms containing variable 5 exon (v5) correlates with enhanced malignancy and invasiveness of some tumors. Here we demonstrate that SRm160, a splicing coactivator, regulates CD44 alternative splicing in a Ras-dependent manner. Overexpression of SRm160 stimulates inclusion of CD44 v5 when Ras is activated. Conversely, small interfering RNA (siRNA)-mediated silencing of SRm160 significantly reduces v5 inclusion. Immunoprecipitation shows association of SRm160 with Sam68, a protein that also stimulates v5 inclusion in a Ras-dependent manner, suggesting that these two proteins interact to regulate CD44 splicing. Importantly, siRNA-mediated depletion of CD44 v5 decreases tumor cell invasion. Reduction of SRm160 by siRNA transfection downregulates the endogenous levels of CD44 isoforms, including v5, and correlates with a decrease in tumor cell invasiveness.

scholarly journals Cell Polarity Factor Par3 Binds SPTLC1 and Modulates Monocyte Serine Palmitoyltransferase Activity and Chemotaxis

2009 ◽  
Vol 284 (37) ◽  
pp. 24881-24890 ◽  
Author(s):  
Norimasa Tamehiro ◽  
Zahedi Mujawar ◽  
Suiping Zhou ◽  
Debbie Z. Zhuang ◽  
Thorsten Hornemann ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Serine Palmitoyltransferase ◽  
Polarity Factor

scholarly journals Modulation of Cellular Migration and Survival by c-Myc through the Downregulation of Urokinase (uPA) and uPA Receptor

2010 ◽  
Vol 30 (7) ◽  
pp. 1838-1851 ◽  
Author(s):  
Daniela Alfano ◽  
Giuseppina Votta ◽  
Almut Schulze ◽  
Julian Downward ◽  
Mario Caputi ◽  
...  
Keyword(s):  
Cell Motility ◽  
Cellular Transformation ◽  
Tumor Formation ◽  
Cellular Migration ◽  
Epithelial Cell Line ◽  
Cellular Motility ◽  
Upa Receptor ◽  
Upar Expression ◽  
Repressive Effect ◽  
Cell Invasiveness

ABSTRACT It has been proposed that c-Myc proapoptotic activity accounts for most of its restraint of tumor formation. We established a telomerase-immortalized human epithelial cell line expressing an activatable c-Myc protein. We found that c-Myc activation induces, in addition to increased sensitivity to apoptosis, reductions in cell motility and invasiveness. Transcriptome analysis revealed that urokinase (uPA) and uPA receptor (uPAR) were strongly downregulated by c-Myc. Evidence is provided that the repression of uPA and uPAR may account for most of the antimigratory and proapoptotic activities of c-Myc. c-Myc is known to cooperate with Ras in cellular transformation. We therefore investigated if this cooperation could converge in the control of uPA/uPAR expression. We found that Ras is able to block the effects of c-Myc activation on apoptosis and cellular motility but not on cell invasiveness. Accordingly, the activation of c-Myc in the context of Ras expression had only minor influence on uPAR expression but still had a profound repressive effect on uPA expression. Thus, the differential regulation of uPA and uPAR by c-Myc and Ras correlates with the effects of these two oncoproteins on cell motility, invasiveness, and survival. In conclusion, we have discovered a novel link between c-Myc and uPA/uPAR. We propose that reductions of cell motility and invasiveness could contribute to the inhibition of tumorigenesis by c-Myc and that the regulation of uPA and uPAR expression may be a component of the ability of c-Myc to reduce motility and invasiveness.

Suppression of Liver Tumor Formation by the Liver Microenvironment of Female, but Not Male, Syngeneic Hosts

2001 ◽  
pp. 489-495
Author(s):  
Gary J. Smith ◽  
Sharon C. Presnell ◽  
William B. Coleman ◽  
Joe W. Grisham
Keyword(s):  
Liver Tumor ◽  
Tumor Formation

scholarly journals Organism-Level Tumor Models in Zebrafish Danio rerio

Acta Naturae ◽  
2018 ◽  
Vol 10 (2) ◽  
pp. 24-29
Author(s):  
I. V. Mizgirev ◽  
D. R. Safina ◽  
I. V. Demidyuk ◽  
S. V. Kostrov
Keyword(s):  
Tumor Cell ◽  
Biomedical Research ◽  
Danio Rerio ◽  
Fluorescent Microscopy ◽  
Tumor Formation ◽  
Transcription Analysis ◽  
New Information ◽  
Optically Transparent ◽  
Tumor Studies ◽  
Effective Models

Development and implementation of adequate organism-level models is one of the key elements in biomedical research that focuses on experimental oncology. Over the last decade, studies using Zebrafish (Danio rerio) have gained in popularity in this area of research. This review describes the various approaches that have been used in developing highly effective models for oncological (clinical term, better cancer or tumor) studies based on D. rerio. Priority is given to transplantation models of cancer and their application to optically transparent D. rerio lines, including clonal ones, and utilization tumors of various origins bearing fluorescent labels. The combination of tumor transplantation at organism-level models in transparent clonal D. rerio lines with fluorescent microscopy, FACS-fractionation of tumor cell subsets, and transcription analysis can result in one of the most promising research approaches in providing new information on tumor formation and growth.

Inhibition of liver tumor cell colonization in two animal tumor models by lectin blocking with D-galactose or arabinogalactan

1988 ◽  
Vol 6 (2) ◽  
pp. 115-120 ◽  
Author(s):  
J. Beuth ◽  
H. L. Ko ◽  
V. Schirrmacher ◽  
G. Uhlenbruck ◽  
G. Pulverer
Keyword(s):  
Tumor Cell ◽  
Liver Tumor ◽  
Tumor Models ◽  
Animal Tumor ◽  
Cell Colonization ◽  
Liver Tumor Cell

scholarly journals Differential regulation of the Hippo pathway by adherens junctions and apical–basal cell polarity modules

2015 ◽  
Vol 112 (6) ◽  
pp. 1785-1790 ◽  
Author(s):  
Chih-Chao Yang ◽  
Hillary K. Graves ◽  
Ivan M. Moya ◽  
Chunyao Tao ◽  
Fisun Hamaratoglu ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Basal Cell ◽  
Mammalian Cells ◽  
Adherens Junctions ◽  
Hippo Pathway ◽  
Tumor Formation ◽  
Nuclear Accumulation ◽  
Binding Motif ◽  
Downstream Effectors ◽  
The Hippo Pathway

Adherens junctions (AJs) and cell polarity complexes are key players in the establishment and maintenance of apical–basal cell polarity. Loss of AJs or basolateral polarity components promotes tumor formation and metastasis. Recent studies in vertebrate models show that loss of AJs or loss of the basolateral component Scribble (Scrib) cause deregulation of the Hippo tumor suppressor pathway and hyperactivation of its downstream effectors Yes-associated protein (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ). However, whether AJs and Scrib act through the same or independent mechanisms to regulate Hippo pathway activity is not known. Here, we dissect how disruption of AJs or loss of basolateral components affect the activity of the Drosophila YAP homolog Yorkie (Yki) during imaginal disc development. Surprisingly, disruption of AJs and loss of basolateral proteins produced very different effects on Yki activity. Yki activity was cell-autonomously decreased but non–cell-autonomously elevated in tissues where the AJ components E-cadherin (E-cad) or α-catenin (α-cat) were knocked down. In contrast, scrib knockdown caused a predominantly cell-autonomous activation of Yki. Moreover, disruption of AJs or basolateral proteins had different effects on cell polarity and tissue size. Simultaneous knockdown of α-cat and scrib induced both cell-autonomous and non–cell-autonomous Yki activity. In mammalian cells, knockdown of E-cad or α-cat caused nuclear accumulation and activation of YAP without overt effects on Scrib localization and vice versa. Therefore, our results indicate the existence of multiple, genetically separable inputs from AJs and cell polarity complexes into Yki/YAP regulation.

666 IMPLICATION OF TRAIL/DR5 INTERNALIZATION IN LIVER TUMOR CELL APOPTOSIS

2011 ◽  
Vol 54 ◽  
pp. S269
Author(s):  
Y. Akazawa ◽  
H. Isomoto ◽  
K. Nakao ◽  
G. Gores
Keyword(s):  
Tumor Cell ◽  
Liver Tumor ◽  
Cell Apoptosis ◽  
Tumor Cell Apoptosis ◽  
Liver Tumor Cell
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