The role of cytoplasmic p57 in invasion of hepatocellular carcinoma.
BACKGROUND
Our previous research suggested that p57 downregulation could accelerate the growth and invasion of hepatocellular carcinoma in vitro and in vivo.


OBJECTIVE
To evaluate the role of cytoplasmic p57 and its regulatory mechanism during hepatocellular carcinoma invasion.


METHODS
We examined the subcellular localization of p57 by immunohistochemistry in 45 pairs of cancerous tissues and adjacent non-cancerous tissues. Moreover, we generated stable p57 knockdown hepatoma cell lines to investigate the mechanism of cytoplasmic p57-mediated regulation of invasion by immunoprecipitation, confocal immunofluorescence microscopy and western blot of nuclear and cytoplasmic extracts.


RESULTS
Our results showed that cytoplasmic expression of p57 was reduced in specimens from patients with capsular invasion and metastasis (P < 0.05). Moreover, the level of p-cofilin was decreased in the group lacking cytoplasmic p57 expression (P < 0.05). Co-expression of p57 and p-cofilin was reduced in specimens from patients with tumors at later stages (III + IV), tumors showing capsular invasion and metastatic tumors. We further observed that p57 downregulation decreased the assembly of p57 and LIM domain kinase 1 and its kinase activity, subsequently reducing the level of p-cofilin in the cytoplasm.


CONCLUSIONS
Cytoplasmic p57 might be a key regulator in hepatocellular carcinoma invasion via the LIM domain kinase 1/p-cofilin pathway.
Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, No. 277 Yanta West Road, Yanta District, Xi'an, Shaanxi Province, 710061, P.R. China. guohuihappy97@163.com.
Hui
H
Guo
Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, No. 277 Yanta West Road, Yanta District, Xi'an, Shaanxi Province, 710061, P.R. China. liyi_712@163.com.
Yi
Y
Li
Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, No. 277 Yanta West Road, Yanta District, Xi'an, Shaanxi Province, 710061, P.R. China. tiantao0607@163.com.
Tao
T
Tian
Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, No. 277 Yanta West Road, Yanta District, Xi'an, Shaanxi Province, 710061, P.R. China. 61439376@qq.com.
Lili
L
Han
Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, No. 277 Yanta West Road, Yanta District, Xi'an, Shaanxi Province, 710061, P.R. China. zopor@163.com.
Zhiping
Z
Ruan
Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, No. 277 Yanta West Road, Yanta District, Xi'an, Shaanxi Province, 710061, P.R. China. elva_0209@126.com.
Xuan
X
Liang
Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, No. 277 Yanta West Road, Yanta District, Xi'an, Shaanxi Province, 710061, P.R. China. wangwenjuan1983@tom.com.
Wenjuan
W
Wang
Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, No. 277 Yanta West Road, Yanta District, Xi'an, Shaanxi Province, 710061, P.R. China. nankj@163.com.
Kejun
K
Nan
D051339:Actin Depolymerizing Factors / Q000032:analysis / Q000378:metabolism; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000473:pathology*; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000737:chemistry; D005260:Female; D020868:Gene Silencing; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000737:chemistry; D008113:Liver Neoplasms / Q000737:chemistry* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness
D051339:Actin Depolymerizing Factors; D050761:Cyclin-Dependent Kinase Inhibitor p57