Bone morphogenetic protein and activin membrane-bound inhibitor overexpression
inhibits gastric tumor cell invasion via the transforming growth
factor-?/epithelial-mesenchymal transition signaling pathway
#MMPMID29805551
Yuan CL
; Liang R
; Liu ZH
; Li YQ
; Luo XL
; Ye JZ
; Lin Y
Exp Ther Med
2018[Jun]; 15
(6
): 5422-5430
PMID29805551
show ga
Gastric carcinoma is one of the most common human malignancies and remains the
second leading cause of cancer-associated mortality worldwide. Gastric carcinoma
is characterized by early-stage metastasis and is typically diagnosed in the
advanced stage. Previous results have indicated that bone morphogenetic protein
and activin membrane-bound inhibitor (BAMBI) overexpression has been demonstrated
to inhibit growth and metastasis of gastric cancer cells. However, the molecular
mechanisms of the BAMBI-mediated signaling pathway in the progression of gastric
cancer are poorly understood. In the present study, to assess whether BAMBI
overexpression inhibited the growth and aggressiveness of gastric carcinoma cells
through regulation of transforming growth factor (TGF)-?/epithelial-mesenchymal
transition (EMT) signaling pathway, the growth and metastasis of gastric
carcinoma cells were analyzed following BAMBI overexpression and knockdown in
vitro and in vivo. Molecular changes in the TGF-?/EMT signaling pathway were
studied in gastric carcinoma cells following BAMBI overexpression and knockdown.
DNA methylation of the gene regions encoding the TGF-?/EMT signaling pathway was
investigated in gastric carcinoma cells. Tumor growth in tumor-bearing mice was
analyzed after mice were subjected to endogenous overexpression of BAMBI. Results
indicated that BAMBI overexpression significantly inhibited gastric carcinoma
cell growth and aggressiveness, whereas knockdown of BAMBI significantly promoted
its growth and metastasis compared with the control (P<0.01). The TGF-?/EMT
signaling pathway was downregulated in BAMBI-overexpressed gastric carcinoma
cells; however, signaling was promoted following BAMBI knockdown. In addition, it
was observed that BAMBI overexpression significantly downregulated the DNA
methylation of the gene regions encoding the TGF-?/EMT signaling pathway
(P<0.01). Furthermore, RNA interference-mediated BAMBI overexpression also
promoted apoptosis in gastric cancer cells and significantly inhibited growth of
gastric tumors in murine xenografts (P<0.01). In conclusion, the present findings
suggest that BAMBI overexpression inhibited the TGF-?/EMT signaling pathway and
suppressed the invasiveness of gastric tumors, suggesting BAMBI may be a
potential target for the treatment of gastric carcinoma via regulation of the
TGF-?/EMT signaling pathway.
free
free
free
