| RRC ID |
44202
|
| Author |
Fujimoto D, Hirono Y, Goi T, Katayama K, Matsukawa S, Yamaguchi A.
|
| Title |
The activation of proteinase-activated receptor-1 (PAR1) promotes gastric cancer cell alteration of cellular morphology related to cell motility and invasion.
|
| Journal |
Int J Oncol
|
| Abstract |
Cell motility proceeds by cycles of edge protrusion, adhesion and retraction. Whether these functions are coordinated by biochemical or biomechanical processes is unknown. Tumor invasion and metastasis is directly related to cell motility. We showed that stimulation of proteinase-activated receptor-1 (PAR1) can trigger an array of responses that would promote tumor cell growth and invasion. Thus, we examined aspects of PAR1 activation related to cell morphological change that might contribute to cell motility. We established a PAR1 stably transfected MKN45 gastric cancer cell line (MKN45/PAR1). We examined morphological changes, Rho family activation and overexpression of cytoskeletal protein in cells exposed to PAR1 agonists (α-thrombin and TFLLR-NH2). MKN45/PAR1 grows with an elongated and polarized morphology, extending pseudopodia at the leading edge. However, in the presence of PAR1 antagonist, MKN45/PAR1 did not show any changes in cell shape upon addition of either α-thrombin or TFLLR-NH2. Activated PAR1 induced RhoA and Rac1 phosphorylation, and subsequent overexpression of myosin IIA and filamin B which are stress fiber components that were identified by PMF analysis of peptide mass data obtained by MALDI-TOF/MS measurement. Upon stimulation of MKN45/PAR1 for 24 h with either α-thrombin or TFLLR-NH2, the distribution of both myosin IIA and filamin B proteins shifted to being distributed throughout the cytoplasm to the membrane, with more intense luminescence signals than in the absence of stimulation. These results demonstrate that PAR1 activation induces cell morphological change associated with cell motility via Rho family activation and cytoskeletal protein overexpression, and has a critical role in gastric cancer cell invasion and metastasis.
|
| Volume |
42(2)
|
| Pages |
565-73
|
| Published |
2013-2-1
|
| DOI |
10.3892/ijo.2012.1738
|
| PMID |
23242308
|
| MeSH |
Cell Line, Tumor
Cell Movement / genetics*
Cytoskeleton / metabolism
Filamins / metabolism
Gene Expression Regulation, Neoplastic / genetics
Humans
Neoplasm Invasiveness / genetics*
Neoplasm Metastasis / genetics
Neoplasm Metastasis / pathology
Nonmuscle Myosin Type IIA / metabolism
Phosphorylation
Receptor, PAR-1 / antagonists & inhibitors
Receptor, PAR-1 / genetics
Receptor, PAR-1 / metabolism*
Stomach Neoplasms / genetics*
Stomach Neoplasms / pathology
rac1 GTP-Binding Protein / metabolism
rhoA GTP-Binding Protein / metabolism
|
| IF |
3.899
|
| Times Cited |
12
|
|
WOS Category
|
ONCOLOGY
|
| Resource |
| Human and Animal Cells |
MKN45(RCB1001)
MKN74(RCB1002) |
