Regulation of cell-cell contact molecules and the metastatic phenotype of medullary thyroid carcinoma by the Raf-1/MEK/ERK pathway.
Surgery
; 144(6): 920-4; discussion 924-5, 2008 Dec.
Article
in En
| MEDLINE
| ID: mdl-19040998
ABSTRACT
BACKGROUND:
Medullary thyroid carcinoma (MTC) is highly metastatic. We have recently reported that activation of the Raf-1/MEK/ERK signaling pathway in MTC cells results in morphologic changes. We hypothesized that Raf-1-induced morphologic changes could be associated with alterations in cell-cell contact molecules, thereby affecting the metastatic potential of MTC cells.METHODS:
An estradiol (E(2))-inducible Raf-1 MTC cell line (TT-raf) was utilized in this study. Western blot analysis was used to confirm the Raf-1/MEK/ERK pathway activation and to measure levels of essential cell-cell contact molecules. Assays for cell adhesion and migration were performed to investigate the cell motility.RESULTS:
E(2) treatment of TT-raf cells resulted in the Raf-1/MEK/ERK pathway activation as evidenced by increased levels of phospho-MEK1/2 and -ERK1/2. This resulted in significant reductions in levels of essential cell-cell contact molecules including E-cadherin, beta-catenin, and occludin. Importantly, activation of the Raf-1/ MEK/ERK pathway and the associated decrease in essential cell-cell contact molecules dramatically inhibited the abilities of adhesion and migration in MTC cells. Furthermore, treatment of Raf-1-activated cells with U0126, a specific inhibitor of MEK, abrogated these Raf-1-induced effects indicating that the suppression of the metastatic phenotype in MTC cells is a MEK-dependent pathway.CONCLUSION:
These data suggest that the Raf-1/MEK/ERK pathway regulates essential cell-cell contact molecules and metastatic phenotype of MTC cells. Thus, these findings provide further insight into the key steps in the metastatic progression of MTC.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thyroid Neoplasms
/
Cell Adhesion Molecules
/
Carcinoma, Medullary
/
Mitogen-Activated Protein Kinase Kinases
/
Mitogen-Activated Protein Kinases
/
Raf Kinases
Limits:
Humans
Language:
En
Journal:
Surgery
Year:
2008
Document type:
Article
Affiliation country: