title: HSP27 modulates epithelial to mesenchymal transition of lung cancer cells in a Smad-independent manner.
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.
authors.affiliation: Department of Internal Medicine, Division of Pulmonary Medicine/Infection and Oncology, Nippon Medical School, Tokyo 113-8603, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Mizutani
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Okano
authors.forename: Yuji
authors.initials: Y
authors.lastname: Minegishi
authors.forename: Kuniko
authors.initials: K
authors.lastname: Matsuda
authors.forename: Junko
authors.initials: J
authors.lastname: Sudoh
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kitamura
authors.forename: Rintaro
authors.initials: R
authors.lastname: Noro
authors.forename: Chie
authors.initials: C
authors.lastname: Soeno
authors.forename: Akinobu
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Seike
authors.forename: Akihiko
authors.initials: A
authors.lastname: Gemma