Activated signal transducer and activator of transcription (STAT) 3: Localization in focal adhesions and function in ovarian cancer cell motility

• Published in: Cancer research (Chicago, Ill.) Ill.), 2004-05, Vol.64 (10), p.3550-3558
• Main Authors: SILVER, Debra L, NAORA, Honami, JINSONG LIU, WENJUN CHENG, MONTELL, Denise J
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Cell Movement - physiology; Cytoskeletal Proteins - metabolism; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - physiology; Epithelial Cells - pathology; Female; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Focal Adhesions - metabolism; Focal Adhesions - pathology; Humans; Medical sciences; Mice; NIH 3T3 Cells; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Paxillin; Pharmacology. Drug treatments; Phosphoproteins - metabolism; Phosphorylation; Protein-Tyrosine Kinases - metabolism; STAT3 Transcription Factor; Trans-Activators - metabolism; Trans-Activators - physiology; Tumors
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-03-3959

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.