Authors: | Azare, J.; Leslie, K.; Al-Ahmadie, H.; Gerald, W.; Weinreb, P. H.; Violette, S. M.; Bromberg, J. |
Article Title: | Constitutively activated stat3 induces tumorigenesis and enhances cell motility of prostate epithelial cells through integrin β6 |
Abstract: | 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 β6 and its ligand, fibronectin (FN). Exogenously added FN increased cellular migration, with a concomitant loss of E-cadherin expression. The blockade of integrin αvβ6 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. Copyright © 2007, American Society for Microbiology. All Rights Reserved. |
Keywords: | immunohistochemistry; signal transduction; controlled study; protein expression; human cell; stat3 protein; cell line, tumor; uvomorulin; prostate cancer; prostatic neoplasms; endothelium cell; cell transformation; prostate epithelium; cell migration; cell movement; cell line, transformed; epithelial cells; stat3 transcription factor; genes, reporter; malignant transformation; luciferases; cadherins; cell motility; clone cells; retroviridae; lamellipodium; fibronectin; colony formation; integrin beta chains; stress fiber; fibronectins; beta6 integrin; pseudopodia; stress fibers |
Journal Title: | Molecular and Cellular Biology |
Volume: | 27 |
Issue: | 12 |
ISSN: | 0270-7306 |
Publisher: | American Society for Microbiology |
Date Published: | 2007-06-01 |
Start Page: | 4444 |
End Page: | 4453 |
Language: | English |
DOI: | 10.1128/mcb.02404-06 |
PUBMED: | 17438134 |
PROVIDER: | scopus |
PMCID: | PMC1900039 |
DOI/URL: | |
Notes: | --- - "Cited By (since 1996): 23" - "Export Date: 17 November 2011" - "CODEN: MCEBD" - "Source: Scopus" |