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Molecular and Cellular Biology, June 2007, p. 4444-4453, Vol. 27, No. 12
0270-7306/07/$08.00+0     doi:10.1128/MCB.02404-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Constitutively Activated Stat3 Induces Tumorigenesis and Enhances Cell Motility of Prostate Epithelial Cells through Integrin ß6 ^,

Departments of Medicine,¹ Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021,² Biogen Idec, Inc., Cambridge, Massachusetts 02142³

Received 22 December 2006/ Returned for modification 16 February 2007/ Accepted 3 April 2007

The persistent activation of signal transducer and activator of transcription 3 (Stat3) is a common feature of prostate cancer. However, little is known about the Stat3 targets that may mediate prostate tumorigenesis. The introduction of an activating mutant form of Stat3 (Stat3-C) into immortalized prostate epithelial cells resulted in tumorigenesis. Stat3-C-expressing cells had decreased E-cadherin levels, increased numbers of lamellipodia and stress fibers, and enhanced migratory capacities compared to vector control-expressing cells, with a concomitant increase in the expression of integrin ß6 and its ligand, fibronectin (FN). Exogenously added FN increased cellular migration, with a concomitant loss of E-cadherin expression. The blockade of integrin vß6 in Stat3-C-expressing cells inhibited migration, increased E-cadherin levels, and reduced colony formation in soft agar. These results demonstrate the sufficiency of constitutively activated Stat3 in mediating prostate tumorigenesis and identify novel Stat3 targets that are involved in promoting cell migration and transformation.

Published ahead of print on 16 April 2007.

Supplemental material for this article may be found at http://mcb.asm.org/.

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