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14‐3‐3ε Induces Epithelial‐Mesenchymal Transition and Suppresses E‐cadherin Expression via Inducing Zeb‐1 in Hepatocellular Carcinoma
Author(s) -
LIU TZUAN,
JAN YEE-JEE,
LIANG SHU-MAN,
KO BOR-SHENG,
LIOU JUN-YANG
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb168
Subject(s) - epithelial–mesenchymal transition , gene knockdown , cadherin , cancer research , metastasis , biology , hepatocellular carcinoma , cell cycle , motility , regulator , apoptosis , cell , microbiology and biotechnology , cancer , gene , genetics
14‐3‐3 proteins are adaptors for assembly multiprotein complexes to regulate a variety of signal pathways. 14‐3‐3 proteins composed of seven isoforms which play crucial roles in regulating multiple cellular processes including the cell cycle regulation, DNA repair, apoptosis, cell adhesion and motility. Our earlier study indicated that increased expression of 14‐3‐3ε is associated with higher rate of tumor metastasis and worse overall survival in hepatocellular carcinoma (HCC). To further investigate the molecular mechanism how 14‐3‐3ε regulate tumor progression, we established 14‐3‐3ε overexpressing HCC stable cells. We found that overexpression of 14‐3‐3ε significantly promoted cell migration, epithelial‐mesenchymal transition (EMT), and transcriptionally repressed E‐cadherin expression in HCC cells. Results from analysis of 14‐3‐3ε/E‐cadherin expression with clinicopathologic characteristics indicates that combination of elevated 14‐3‐3ε expression with reduced E‐cadherin expression is correlated with higher incidence of HCC metastasis and poor 5‐year overall survival. Moreover, overexpression of 14‐3‐3ε significantly induced Snail and Zeb‐1 expression, however, the effect of 14‐3‐3ε‐reduced E‐cadherin was specifically restored by knockdown of Zeb‐1 but not Snail with their specific siRNA. Taken together, 14‐3‐3ε may act as an important regulator to modulate tumor metastasis by promoting EMT as well as migration, and serve as a potentially prognostic biomarker and therapeutic target for HCC.