Interferon consensus sequence-binding protein (ICSBP) promotes
epithelial-to-mesenchymal transition (EMT)-like phenomena, cell-motility, and
invasion via TGF-? signaling in U2OS cells
#MMPMID24832596
Sung JY
; Park SY
; Kim JH
; Kang HG
; Yoon JH
; Na YS
; Kim YN
; Park BK
Cell Death Dis
2014[May]; 5
(5
): e1224
PMID24832596
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Interferon consensus sequence-binding protein (ICSBP) is a transcription factor
induced by interferon gamma (IFN-?) and a member of the interferon regulatory
factor (IRF) family. ICSBP is predominantly expressed in hematopoietic cells and
regulates the immune response and cell growth and differentiation. However,
little is known about its function in non-hematopoietic cells. Here we show a
novel function for ICSBP in epithelial-to-mesenchymal transition (EMT)-like
phenomena (ELP), cell motility, and invasion in human osteosarcoma cell lines,
including U2OS cells. IFN-? treatment induced ICSBP expression and EMT-like
morphological change in U2OS cells, which were suppressed by ICSBP knockdown. To
further investigate the role of ICSBP in ELP, we established a stable U2OS cell
line that overexpresses ICSBP. ICSBP expression caused U2OS cells to have a more
elongated shape and an increased vimentin and fibronectin expression. ICSBP
expression also promoted adhesiveness, motility, and invasiveness of U2OS cells.
ICSBP upregulated transforming growth factor (TGF)-? receptors and activated
TGF-? signaling cascades, which were responsible for ELP as well as increased
cell motility and invasion. In addition, ICSBP-induced TGF-? receptor activation
resulted in the upregulation of Snail. Knockdown of Snail attenuated the
ICSBP-induced augmentation of cell motility and invasion. Upregulation of Snail,
ELP, and increased invasion by ICSBP expression were also observed in other
osteosarcoma cell lines, such as Saos-2 and 143B. Furthermore, ICSBP and TGF-?
receptor I were expressed in 45/54 (84%) and 47/54 (87%) of human osteosarcoma
tissues, respectively, and showed significant correlation (r=0.47, P=0.0007) with
respect to their expression levels. Taken altogether, these data demonstrate a
novel function for ICSBP in ELP, cell motility, and invasion through the TGF-?
and Snail signaling pathways.
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