Journal Article

CANCER BIOLOGY: The antitumor drug fostriecin induces vimentin hyperphosphorylation and intermediate filament reorganization

Duncan T. Ho and Michel Roberge

in Carcinogenesis

Volume 17, issue 5, pages 967-972
Published in print May 1996 | ISSN: 0143-3334
e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.5.967
CANCER BIOLOGY: The antitumor drug fostriecin induces vimentin hyperphosphorylation and intermediate filament reorganization

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Fostriecin is an antitumor drug in phase I clinical trials. We have recently shown that it is a potent inhibitor of protein phosphatases 1 and 2A in vitro, a property not previously described for an antitumor drug. We have investigated its effects on protein phosphorylation in baby hamster kidney cells. Fostriecin strongly stimulated the phosphorylation of a single protein, which we identified as the intermediate filament vimentin. Fostriecin also caused rounding of the cells and a reorganization of the vimentin filaments. These effects are similar to those of the known protein phosphatase 1 and 2A inhibitors okadaic acid and calyculin A, which are also tumor promoters. Fostriecin induced vimentin hyperphosphorylation mostly at two sites, which were sensitive to staurosporine and could be phos-phorylated by protein kinase C in vitro. Fostriecin-induced vimentin hyperphosphorylation also occurred in cells that lack p34Ccdc2 kinase activity. These results suggest that protein kinase C plays a direct or indirect role in vimentin hyperphosphorylation during exposure to fostriecin. The results also provide strong evidence that fostriecin inhibits protein phosphatases 1 and 2A in vivo and raise the possibility that it may have tumor-promoting activity.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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