Knockdown of ZEB1, a master epithelial-to-mesenchymal transition (EMT) gene, suppresses anchorage-independent cell growth of lung cancer cells.
We found that among four master epithelial-to-mesenchymal transition (EMT)-inducing genes (ZEB1, SIP1, Snail, and Slug) ZEB1expression was most significantly correlated with the mesenchymal phenotype (high Vimentin and low E-cadherin expression) in non-small cell lung cancer (NSCLC) cell lines and tumors. Furthermore, ZEB1 knockdown with RNA interference in three NSCLC cell lines with high ZEB1 expression suppressed to varying degrees mass culture growth and liquid colony formation but in all cases dramatically suppressed soft agar colony formation. In addition, ZEB1 knockdown induced apoptosis in one of the three lines, indicating that the growth inhibitory effects of ZEB1 knockdown occurs in part through the activation of the apoptosis pathway. These results suggest that inhibiting ZEB1 function may be an attractive target for NSCLC therapeutic development.
Takeyama
Yoshihiro
Y
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Sato
Mitsuo
M
Horio
Mihoko
M
Hase
Tetsunari
T
Yoshida
Kenya
K
Yokoyama
Toshihiko
T
Nakashima
Harunori
H
Hashimoto
Naozumi
N
Sekido
Yoshitaka
Y
Gazdar
Adi F
AF
Minna
John D
JD
Kondo
Masashi
M
Hasegawa
Yoshinori
Y
D017209:Apoptosis / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002455:Cell Division; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008648:Mesoderm / Q000473:pathology; D008654:Mesothelioma / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics; D009154:Mutation; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014746:Vimentin / Q000235:genetics; D000071799:Zinc Finger E-box-Binding Homeobox 1
D015820:Cadherins; D018398:Homeodomain Proteins; D035683:MicroRNAs; D034741:RNA, Small Interfering; D014157:Transcription Factors; D014746:Vimentin; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D066246:ErbB Receptors
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