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Sphingosine 1-phosphate and human ether-a'-go-go related gene (HERG) potassium channel modulate migration in human anaplastic thyroid cancer cells.
MedLine Citation:
PMID:  22889737     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Ananplastic thyroid cancer (ATC) is the most aggressive form of human thyroid cancer, lacking any effective treatment. Sphingosine 1-phosphate (S1P) receptors and human ether-a-go-go related gene (HERG) potassium channels are important modulators of cell migration. In the present study, we have shown that the S1P1-3 receptors are expressed in C643 and THJ-16T human anaplastic thyroid cancer cell lines, both at mRNA and protein level. S1P inhibited migration of these cells and of follicular FTC-133 thyroid cancer cells. Using the S1P1,3 inhibitor VPC-23019, the S1P2 inhibitor JTE-013 and S1P2 receptor siRNA, we showed that the effect was mediated through S1P2. Treatment of the cells with the Rho inhibitor C3 transferase, abolished the effect of S1P on migration. S1P attenuated Rac activity, and inhibiting Rac decreased migration. Sphingosine kinase inhibitor enhanced basal migration of cells, and addition of exogenous S1P inhibited migration. C643 cells expressed a non-conducting HERG protein, and S1P decreased HERG protein expression. The HERG blocker E-4031 decreased migration. Interestingly, down-regulating HERG protein with siRNA, decreased the basal migration. In experiments using HEK cells overexpressing HERG, we showed that S1P decreased channel protein expression and current, and that S1P attenuated migration of the cells. We conclude that S1P attenuates migration of C643 anaplastic thyroid cancer cells by activating S1P2 and the Rho pathway. The attenuated migration is also, in part, dependent on a S1P-induced decrease of HERG protein.
Authors:
Muhammad Yasir Asghar; Tero Viitanen; Kati Kemppainen; Kid Törnquist
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-13
Journal Detail:
Title:  Endocrine-related cancer     Volume:  -     ISSN:  1479-6821     ISO Abbreviation:  Endocr. Relat. Cancer     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9436481     Medline TA:  Endocr Relat Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
M Asghar, Department of Biosciences, Åbo Akademi University, Turku, Finland.
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