scholarly journals Regulators of Actin Dynamics in Gastrointestinal Tract Tumors

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Konrad Steinestel ◽  
Eva Wardelmann ◽  
Wolfgang Hartmann ◽  
Inga Grünewald

Reorganization of the actin cytoskeleton underlies cell migration in a wide variety of physiological and pathological processes, such as embryonic development, wound healing, and tumor cell invasion. It has been shown that actin assembly and disassembly are precisely regulated by intracellular signaling cascades that respond to changes in the cell microenvironment, ligand binding to surface receptors, or oncogenic transformation of the cell. Actin-nucleating and actin-depolymerizing (ANFs/ADFs) and nucleation-promoting factors (NPFs) regulate cytoskeletal dynamics at the leading edge of migrating cells, thereby modulating cell shape; these proteins facilitate cellular movement and mediate degradation of the surrounding extracellular matrix by secretion of lytic proteases, thus eliminating barriers for tumor cell invasion. Accordingly, expression and activity of these actin-binding proteins have been linked to enhanced metastasis and poor prognosis in a variety of malignancies. In this review, we will summarize what is known about expression patterns and the functional role of actin regulators in gastrointestinal tumors and evaluate first pharmacological approaches to prevent invasion and metastatic dissemination of malignant cells.

2006 ◽  
Vol 26 (4) ◽  
pp. 1480-1495 ◽  
Author(s):  
Heather J. Spence ◽  
Lynn McGarry ◽  
Catherine S. Chew ◽  
Neil O. Carragher ◽  
Linda A. Scott-Carragher ◽  
...  

ABSTRACT The transcription factor AP-1, which is composed of Fos and Jun family proteins, plays an essential role in tumor cell invasion by altering gene expression. We report here that Krp1, the AP-1 up-regulated protein that has a role in pseudopodial elongation in v-Fos-transformed rat fibroblast cells, forms a novel interaction with the nondifferentially expressed actin binding protein Lasp-1. Krp1 and Lasp-1 colocalize with actin at the tips of pseudopodia, and this localization is maintained by continued AP-1 mediated down-regulation of fibronectin that in turn suppresses integrin and Rho-ROCK signaling and allows pseudopodial protrusion and mesenchyme-like invasion. Mutation analysis of Lasp-1 demonstrates that its SH3 domain is necessary for pseudopodial extension and invasion. The results support the concept of an AP-1-regulated multigenic invasion program in which proteins encoded by differentially expressed genes direct the function, localization, and activity of proteins that are not differentially expressed to enhance the invasiveness of cells.


2004 ◽  
Vol 42 (08) ◽  
Author(s):  
P Michl ◽  
M Ei'Bahrawy ◽  
R Poulsom ◽  
A Ramjaun ◽  
J Downward

BIO-PROTOCOL ◽  
2012 ◽  
Vol 2 (3) ◽  
Author(s):  
Yanling Chen

2006 ◽  
Vol 26 (1) ◽  
pp. 362-370 ◽  
Author(s):  
Chonghui Cheng ◽  
Phillip A. Sharp

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.


2010 ◽  
Vol 63 (9) ◽  
pp. 563-565 ◽  
Author(s):  
Yasuhiro Igarashi ◽  
Ryoko Shimasaki ◽  
Satoshi Miyanaga ◽  
Naoya Oku ◽  
Hiroyasu Onaka ◽  
...  

2008 ◽  
Vol 68 (18) ◽  
pp. 7371-7379 ◽  
Author(s):  
John M. Lamar ◽  
Kevin M. Pumiglia ◽  
C. Michael DiPersio

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