Smad4 is essential for down-regulation of E-cadherin induced by TGF-beta in pancreatic cancer cell line PANC-1.
Smad4 is a tumour suppressor gene frequently deleted in pancreatic cancer. To investigate the roles of Smad4 deficiency in invasive and matastatic capabilities of pancreatic cancer, we examined the effects of Smad4 deficiency on regulation of the invasion suppressor E-cadherin in pancreatic cancer cell line PANC-1. TGF-beta decreased expression of E-cadherin and beta-catenin proteins at the plasma membrane, increased Snail and Slug mRNA expression, and induced fibroblastoid morphology in PANC-1 cells. These effects of TGF-beta were abrogated in Smad4-knocked-down PANC-1 cells. We also found that TGF-beta-induced down-regulation of E-cadherin expression was partially inhibited in Snail- and Slug-knocked-down PANC-1 cells. Thus, Smad4 mediates down-regulation of E-cadherin induced by TGF-beta in PANC-1 cells, at least in part, through Snail and Slug induction. These results suggest that Smad4 deficiency observed in invasive and metastatic pancreatic cancer might not be linked to the loss of E-cadherin.
Takano
Shinichi
S
Department of Immunology, University of Yamanashi, Yamanashi 409-3898, Japan.
Kanai
Fumihiko
F
Jazag
Amarsanaa
A
Ijichi
Hideaki
H
Yao
Jian
J
Ogawa
Hideoki
H
Enomoto
Nobuyuki
N
Omata
Masao
M
Nakao
Atsuhito
A
D015820:Cadherins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D051900:Smad3 Protein / Q000172:deficiency; D051901:Smad4 Protein / Q000172:deficiency / Q000502:physiology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000172:deficiency; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D015820:Cadherins; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; C000604407:SNAI1 protein, human; D051900:Smad3 Protein; D051901:Smad4 Protein; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A