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

Mizutani,Hideaki; Okano,Tetsuya; Minegishi,Yuji; Matsuda,Kuniko; Sudoh,Junko; Kitamura,Kazuhiro; Noro,Rintaro; Soeno,Chie; Yoshimura,Akinobu; Seike,Masahiro; Gemma,Akihiko

doi:10.3892/ol.2010.190

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

Authors:
- Hideaki Mizutani
- Tetsuya Okano
- Yuji Minegishi
- Kuniko Matsuda
- Junko Sudoh
- Kazuhiro Kitamura
- Rintaro Noro
- Chie Soeno
- Akinobu Yoshimura
- Masahiro Seike
- Akihiko Gemma
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Affiliations: Department of Internal Medicine, Division of Pulmonary Medicine/Infection and Oncology, Nippon Medical School, Tokyo 113-8603, Japan
Published online on: September 23, 2010 https://doi.org/10.3892/ol.2010.190
Pages: 1011-1016

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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.

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