Article

The role of Lamin A in cytoskeleton organization in colorectal cancer cells: a proteomic investigation.

School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK.
Nucleus (Austin, Texas) 09/2011; 2(5):434-43. DOI:10.4161/nucl.2.5.17775 pp.434-43
Source: PubMed

ABSTRACT Up-regulated expression of lamin A has been implicated in increased cell invasiveness and mortality in colorectal cancer. Here we use quantitative proteomics to investigate lamin A regulated changes in the cytoskeleton that might underpin increased cell motility. Using siRNA knockdown of lamin A in a model cell line (SW480/lamA) we confirm that the presence of lamin A promotes cell motility. Using an enhanced technique to prepare cytoskeleton fractions in combination with 2D DiGE we were able to accurately and reproducibly detect changes in the representation of protein species within the cytoskeleton as low as 20%. In total 64 protein spots displayed either increased or decreased representation within the cytoskeleton of SW480/lamA cells compared to controls. Of these the identities of 29 spots were determined by mass spectrometry. A majority were multiple forms of three classes of proteins, including components of the actin and IF cytoskeletons, protein chaperones and translation initiation and elongation factors. In particular our data reveal that the representation of tissue transglutaminase 2, which is known to modify elements of the cytoskeleton and is associated with cancer progression, was highly over-represented in the cytoskeleton fraction of SW480/lamA cells. Overall, our data are consistent with changed protein cross-linking and folding that favours the formation of dynamic actin filaments over stress fibres accounting for the altered cell motility properties in SW480/lamA cells.

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Keywords

actin
 
altered cell motility properties
 
cancer progression
 
cell invasiveness
 
cell motility
 
colorectal cancer
 
cytoskeleton fraction
 
cytoskeleton fractions
 
dynamic actin filaments
 
elongation factors
 
mass spectrometry
 
model cell line
 
promotes cell motility
 
protein chaperones
 
protein cross-linking
 
regulated changes
 
siRNA knockdown
 
stress fibres accounting
 
tissue transglutaminase 2
 
total 64 protein spots