Interferon consensus sequence-binding protein (ICSBP) promotes epithelial-to-mesenchymal transition (EMT)-like phenomena, cell-motility, and invasion via TGF-β signaling in U2OS cells.
Interferon consensus sequence-binding protein (ICSBP) is a transcription factor induced by interferon gamma (IFN-γ) 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-γ 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)-β receptors and activated TGF-β signaling cascades, which were responsible for ELP as well as increased cell motility and invasion. In addition, ICSBP-induced TGF-β 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-β 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-β and Snail signaling pathways.
Center for Pediatric Oncology, National Cancer Center, Goyang-si, Gyeonggi-do, Korea.
J Y
JY
Sung
Department of Pathology, National Cancer Center, Goyang-si, Gyeonggi-do, Korea.
S-Y
SY
Park
Orthopaedic Oncology Clinic, National Cancer Center, Goyang-si, Gyeonggi-do, Korea.
J H
JH
Kim
Orthopaedic Oncology Clinic, National Cancer Center, Goyang-si, Gyeonggi-do, Korea.
H G
HG
Kang
Center for Pediatric Oncology, National Cancer Center, Goyang-si, Gyeonggi-do, Korea.
J H
JH
Yoon
Center for Pediatric Oncology, National Cancer Center, Goyang-si, Gyeonggi-do, Korea.
Y S
YS
Na
Comparative Biomedicine Research Branch, National Cancer Center, Goyang-si, Gyeonggi-do, Korea.
Y-N
YN
Kim
Center for Pediatric Oncology, National Cancer Center, Goyang-si, Gyeonggi-do, Korea.
B-K
BK
Park
D015703:Antigens, CD; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D018920:Coculture Techniques; D058750:Epithelial-Mesenchymal Transition; D005353:Fibronectins / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism; D000099185:Interferon Regulatory Factor-8
D015703:Antigens, CD; D015820:Cadherins; D005353:Fibronectins; D050835:Interferon Regulatory Factors; D007371:Interferon-gamma; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D014746:Vimentin; D000099185:Interferon Regulatory Factor-8; C513384:CDH1 protein, human