Involvement of focal adhesion kinase in inhibition of motility of human breast cancer cells by sphingosine 1-phosphate

Wang, Fang, Nohara, Keiko, Olivera, Ana, Thompson, Erik W., & Spiegel, Sarah (1999) Involvement of focal adhesion kinase in inhibition of motility of human breast cancer cells by sphingosine 1-phosphate. Experimental Cell Research, 247(1), pp. 17-28.

View at publisher


Sphingosine 1-phosphate (SPP), a bioactive sphingolipid metabolite, inhibits chemoinvasiveness of the aggressive, estrogen-independent MDA-MB-231 human breast cancer cell line. As in many other cell types, SPP stimulated proliferation of MDA-MB-231 cells, albeit to a lesser extent. Treatment of MDA-MB-231 cells with SPP had no significant effect on their adhesiveness to Matrigel, and only high concentrations of SPP partially inhibited matrix metalloproteinase-2 activation induced by Con A. However, SPP at a concentration that strongly inhibited invasiveness also markedly reduced chemotactic motility. To investigate the molecular mechanisms by which SPP interferes with cell motility, we examined tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin, which are important for organization of focal adhesions and cell motility. SPP rapidly increased tyrosine phosphorylation of FAK and paxillin and of the paxillin-associated protein Crk. Overexpression of FAK and kinase-defective FAK in MDA-MB-231 cells resulted in a slight increase in motility without affecting the inhibitory effect of SPP, whereas expression of FAK with a mutation of the major autophosphorylation site (F397) abolished the inhibitory effect of SPP on cell motility. In contrast, the phosphoinositide 3'-kinase inhibitor, wortmannin, inhibited chemotactic motility in both vector and FAK-F397- transfected cells. Our results suggest that autophosphorylation of FAK on Y397 may play an important role in SPP signaling leading to decreased cell motility.

Impact and interest:

61 citations in Scopus
Search Google Scholar™
61 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 72177
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996):61 Export Date: 6 May 2014 Source: Scopus PubMed ID: 10047444
Additional URLs:
DOI: 10.1006/excr.1998.4327
ISSN: 0014-4827
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 28 May 2014 01:43
Last Modified: 28 May 2014 01:43

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page