Article

HSP27 modulates epithelial to mesenchymal transition of lung cancer cells in a Smad-independent manner.

Department of Internal Medicine, Division of Pulmonary Medicine/Infection and Oncology, Nippon Medical School, Tokyo 113-8603, Japan.
Oncology letters (impact factor: 0.11). 11/2010; 1(6):1011-1016. DOI:10.3892/ol.2010.190 pp.1011-1016
Source: PubMed

ABSTRACT Epithelial to mesenchymal transition (EMT) is induced by transforming growth factor-β1 (TGF-β1) and is a crucial event for cancer cells to acquire invasive and metastatic phenotypes. However, the signals that induce EMT in cancer cells have yet to be adequately defined. In this study, a proteomic investigation was performed to understand the signaling pathway of the EMT of lung cancer using two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry. The protein expression profiles of A549 were compared to those of A549 cells treated with TGF-β1. Of more than 2,000 protein spots shown by 2D-DIGE, 53 were found to be up- or down-regulated upon induction with TGF-β1. In the 53 protein spots, the protein level of heat shock protein (HSP) 27 was found to increase significantly. HSP27 protein was higher in two different lung cancer cell lines, demonstrating the EMT phenomenon with TGF-β1. Notably, the silencing of HSP27 enhanced spindle integration, resulting in an additive effect with TGF-β1-induced EMT. Furthermore, the TGF-β1-induced HSP27 increase was not affected by the suppression of Smad2 and Smad3 in A549 cells. These results suggest that HSP27 was involved in TGF-β1-induced EMT in a Smad-independent manner in lung cancer cells and may provide an effective clinical strategy in lung cancer patients whose tumors are dependent on TGF-β1-induced EMT.

0 0
 · 
0 Bookmarks
 · 
20 Views
  • Article: Identification and characterization of hic-5/ARA55 as an hsp27 binding protein.
    Y Jia, R F Ransom, M Shibanuma, C Liu, M J Welsh, W E Smoyer
    [show abstract] [hide abstract]
    ABSTRACT: hsp27 has been reported to participate in a wide variety of activities, including resistance to thermal and metabolic stress, regulation of growth and differentiation, and acting as a molecular chaperone or a regulator of actin polymerization. We hypothesized that these diverse functions are regulated in a cell- or tissue-specific manner via interaction with various binding proteins. To investigate this hypothesis, we used hsp27 as a "bait" to screen a yeast two-hybrid cDNA library from rat kidney glomeruli and identified a novel hsp27 binding protein, hic-5 (also known as ARA55), a focal adhesion protein and steroid receptor co-activator. Biochemical interaction between hsp27 and hic-5 was confirmed by co-immunoprecipitation, and critical protein.protein interaction regions were mapped to the hic-5 LIM domains and the hsp27 C-terminal domain. Initial analysis of the functional role of hsp27.hic-5 interaction revealed that hic-5 significantly inhibited the protection against heat-induced cell death conferred by hsp27 overexpression in co-transfected 293T cells. In contrast, when a non-hsp27-interacting hic-5 truncation mutant (hic-5/DeltaLIM4) was co-expressed with hsp27, the hic-5 inhibition of hsp27 protection was absent. We conclude that hic-5 is a true hsp27 binding protein and inhibits the ability of hsp27 to provide protection against heat shock in an interaction-dependent manner.
    Journal of Biological Chemistry 11/2001; 276(43):39911-8. · 4.77 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

53 protein spots
 
additive effect
 
cancer cells
 
crucial event
 
different lung cancer cell lines
 
effective clinical strategy
 
EMT phenomenon
 
heat shock protein
 
HSP27 protein
 
induce EMT
 
lung cancer
 
lung cancer cells
 
lung cancer patients
 
mesenchymal transition
 
protein expression profiles
 
Smad-independent manner
 
spindle integration
 
TGF-β1-induced EMT
 
TGF-β1-induced HSP27 increase
 
two-dimensional difference gel electrophoresis