title: Constitutively activated Stat3 induces tumorigenesis and enhances cell motility of prostate epithelial cells through integrin beta 6.
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 beta6 and its ligand, fibronectin (FN). Exogenously added FN increased cellular migration, with a concomitant loss of E-cadherin expression. The blockade of integrin alphavbeta6 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.
authors: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors: Janeen
authors: J
authors: Azare
authors: Kenneth
authors: K
authors: Leslie
authors: Hikmat
authors: H
authors: Al-Ahmadie
authors: William
authors: W
authors: Gerald
authors: Paul H
authors: PH
authors: Weinreb
authors: Shelia M
authors: SM
authors: Violette
authors: Jacqueline
authors: J
authors: Bromberg
mesh_terms: D015820:Cadherins / Q000032:analysis / Q000378:metabolism; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002999:Clone Cells; D004847:Epithelial Cells / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D007150:Immunohistochemistry; D039641:Integrin beta Chains / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000209:etiology* / Q000473:pathology; D011554:Pseudopodia / Q000502:physiology; D012190:Retroviridae / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D022502:Stress Fibers / Q000502:physiology
chemical_list: D015820:Cadherins; D005353:Fibronectins; D039641:Integrin beta Chains; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C072170:integrin beta6; D008156:Luciferases