title: Kindlin-2 promotes invasiveness of prostate cancer cells via NF-κB-dependent upregulation of matrix metalloproteinases.
abstract: Invasive progression is the major lethal cause of prostate cancer. In this study, we aimed to investigate the role of kindlin-2, an integrin-binding focal adhesion protein, in the regulation of invasiveness of prostate cancer. We found that downregulation of kindlin-2 using small interfering RNA (siRNA) technology significantly inhibited the invasion of PC-3 and DU-145 prostate cancer cells in a Matrigel Transwell assay. Conversely, overexpression of kindlin-2 promoted the invasiveness of prostate cancer cells. Kindlin-2 overexpression was found to activate nuclear factor (NF)-κB-dependent signaling and upregulate the expression of matrix metalloproteinase-9 (MMP-9) and MMP-2, whereas kindlin-2 silencing led to opposing effects on the expression of NF-κB and MMPs. Most importantly, kindlin-2-induced invasiveness was almost completely abolished by pretreatment with pyrrolidine dithiocarbamate (an inhibitor of NF-κB signaling) or co-transfection with MMP-9 or MMP-2 siRNA. Taken together, our data indicate that kindlin-2 promotes the invasiveness of prostate cancer cells largely through NF-κB-dependent upregulation of MMP-9 and MMP-2. Further studies are warranted to evaluate the significance of kindlin-2 as a therapeutic target for metastatic prostate cancer.
authors.affiliation: Department of Urology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, China.
authors.forename: Jia-rong
authors.initials: JR
authors.lastname: Yang
authors.affiliation: Department of Urology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, China. Electronic address: tiejunpan2010@163.com.
authors.forename: Tie-jun
authors.initials: TJ
authors.lastname: Pan
authors.affiliation: Department of Urology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Urology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Urology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Urology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Urology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, China.
authors.forename: Wei-hong
authors.initials: WH
authors.lastname: Qian
mesh_terms: D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008565:Membrane Proteins / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: C477322:FERMT3 protein, human; D008565:Membrane Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Genetic manipulation; Kindlin-2; Metastasis; NF-κB signaling; Prostate cancer