TGF-β induces fascin expression in gastric cancer via phosphorylation of smad3 linker area.
BACKGROUND
Fascin is an actin-bundling protein critical for tumor invasion. TGF-β could induce fascin expression in gastric cancer cells. In this study, we attempted to explore the role of p-smad3L in the expression of fascin induced by TGF-β in gastric cancer cells.


METHODS
Pseudopodia were evaluated by immunofluorescence. Fascin expression was detected by RT-PCR and western blot. Smad3 siRNA was used to repress the endogenous smad3. The phosphorylations of smad3 linker region at sites s204, s208 and s213 were detected by western blot. The fascin promoter reporter activity was measured by dual luciferase assay.


RESULTS
TGF-β could increase the formation of pseudopodia and the expression of fascin in gastric cancer cells. Smad3 depletion abrogated the expression of fascin induced by TGF-β. The phosphorylation of smad3 linker region at serine 204, 208 and 213 was enhanced in gastric cancer cells after TGF-β treatment. The fascin promoter reporter activity was significantly enhanced with TGF-β treatment in both wild-type Smad3 group and Smad3EPSM group (P<0.05). Furthermore, the fascin promoter reporter activity in the wild-type Smad3 transfectant cells was significantly higher than that in Smad3EPSM cells (P<0.05).


CONCLUSIONS
fascin expression induced by TGF-β depends on smad3, at least in part, depends on smad3 linker phosphorylation.
Department of Pathology, Xiangya Hospital, Central South University Changsha, China ; Department of Pathology, Xiangya Medical School, Central South University Changsha, China.
Liling
L
Li
Department of Pathology, Xiangya Hospital, Central South University Changsha, China ; Department of Pathology, Xiangya Medical School, Central South University Changsha, China.
Fang
F
Cao
Department of Pathology, Xiangya Hospital, Central South University Changsha, China ; Department of Pathology, Xiangya Medical School, Central South University Changsha, China.
Baoan
B
Liu
Department of Pathology, Xiangya Hospital, Central South University Changsha, China ; Department of Pathology, Xiangya Medical School, Central South University Changsha, China.
Xiaojuan
X
Luo
Department of Pathology, Xiangya Hospital, Central South University Changsha, China ; Department of Pathology, Xiangya Medical School, Central South University Changsha, China.
Xin
X
Ma
Department of Pathology, Xiangya Hospital, Central South University Changsha, China ; Department of Pathology, Xiangya Medical School, Central South University Changsha, China.
Zhongliang
Z
Hu
TGF-β; fascin; gastric cancer; smad3