CD147 promotes cell motility via upregulation of p190-B RhoGAP in hepatocellular carcinoma.
BACKGROUND
The acquisition of inappropriate migratory feature is crucial for tumor metastasis. Rho-family GTPases including RhoA are molecular switches that play critical roles in regulating cell movement. We investigated the molecular mechanism underlying CD147 induced RhoA deactivation in hepatocellular carcinoma (HCC) cells.


METHODS
Wound-healing assay was performed to study the cell motility. Analysis of RhoA activation in living cells was conducted using RhoA biosensor. Changes in the expression of certain genes were determined by quantitative real-time PCR. The expression of proteins was evaluated by Western blot. Cytoskeleton reorganization and focal adhesion formation were observed by immunofluorescence staining. Further investigation on the correlation between CD147 and p190-B RhoGAP (p190-B) in HCC tissues was performed by immunological histological chemistry analysis.


RESULTS
CD147 promoted cell movement and suppressed RhoA activation. p190-B, a negative regulator of RhoA activity, was upregulated by CD147 at both mRNA and protein levels. This regulatory relationship was further confirmed by analyzing the expression pattern of CD147 and p190-B in human HCC tissues. Silencing of p190-B caused the increased formation of stress fiber and focal adhesion and blunted the impact of CD147 overexpression on cell movement, indicating that the regulatory effect of CD147 on cell movement is mediated, at least partially, by p190-B.


CONCLUSIONS
These findings indicated that p190-B, a negative regulator of RhoA, is positively regulated by CD147 and contributes to the regulation of cell movement in HCC. CD147 plays critical roles in the motility of cancer cells and may be therefore a valuable drug target for anti-cancer therapy.
Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, 710032 People's Republic of China.|Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, 510632 People's Republic of China.
Ruo
R
Chen
Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, 710032 People's Republic of China.
Shi-Jie
SJ
Wang
Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, 710032 People's Republic of China.
Yang
Y
Zhang
Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, 710032 People's Republic of China.
Rong
R
Hou
Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, 710032 People's Republic of China.
Jian-Li
JL
Jiang
Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, 710032 People's Republic of China.
Hong-Yong
HY
Cui
CD147; Cell movement; Hepatocellular carcinoma; RhoA; p190-B RhoGAP