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[Cancer Research 64, 3550-3558, May 15, 2004]
© 2004 American Association for Cancer Research

Regular Articles

Activated Signal Transducer and Activator of Transcription (STAT) 3

Localization in Focal Adhesions and Function in Ovarian Cancer Cell Motility

Debra L. Silver1, Honami Naora2, Jinsong Liu3, Wenjun Cheng2 and Denise J. Montell1

1 Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland, and Departments of 2 Molecular Therapeutics and 3 Pathology, University of Texas M. D. Anderson Cancer Center, Houston, Texas

Constitutive activation of the Janus-activated kinase/signal transducer and activator of transcription (STAT) pathway promotes the proliferation and survival of cancer cells in culture and is associated with various cancers, including those of the ovary. We found that constitutively activated STAT3 levels correlated with aggressive clinical behavior of ovarian carcinoma specimens. Furthermore, inhibition of STAT3 reduced the motility of ovarian cancer cells in vitro. Surprisingly, we found that activated STAT3 localized not only to nuclei but also to focal adhesions in these cells. Activated STAT3 coimmunoprecipitated with phosphorylated paxillin and focal adhesion kinase and required paxillin and Src for its localization to focal adhesions. These results suggest that Janus-activated kinase/STAT signaling may contribute to ovarian cancer cell invasiveness.




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