title: LIM kinase1 modulates function of membrane type matrix metalloproteinase 1: implication in invasion of prostate cancer cells.
abstract: BACKGROUND
  LIM kinase 1 (LIMK1) is an actin and microtubule cytoskeleton modulatory protein that is overexpressed in a number of cancerous tissues and cells and also promotes invasion and metastasis of prostate and breast cancer cells. Membrane type matrix metalloproteinase 1 (MT1-MMP) is a critical modulator of extracellular matrix (ECM) turnover through pericellular proteolysis and thus plays crucial roles in neoplastic cell invasion and metastasis. MT1-MMP and its substrates pro-MMP-2 and pro-MMP-9 are often overexpressed in a variety of cancers including prostate cancer and the expression levels correlate with the grade of malignancy in prostate cancer cells. The purpose of this study is to determine any functional relation between LIMK1 and MT1-MMP and its implication in cell invasion.
  
  
  RESULTS
  Our results showed that treatment with the hydroxamate inhibitor of MT1-MMP, MMP-2 and MMP-9 ilomastat inhibited LIMK1-induced invasion of benign prostate epithelial cells. Over expression of LIMK1 resulted in increased collagenolytic activity of MMP-2, and secretion of pro-MMP2 and pro-MMP-9. Cells over expressing LIMK1 also exhibited increased expression of MT1-MMP, transcriptional activation and its localization to the plasma membrane. LIMK1 physically associates with MT1-MMP and is colocalized with it to the Golgi vesicles. We also noted increased expression of both MT1-MMP and LIMK1 in prostate tumor tissues.
  
  
  CONCLUSIONS
  Our results provide new information on regulation of MT1-MMP function by LIMK1 and showed for the first time, involvement of MMPs in LIMK1 induced cell invasion.
authors.affiliation: Department of Molecular Biology and Microbiology, Burnett School of Biomolecular Sciences, University of Central Florida, Orlando, FL, USA.
authors.forename: Tenekua
authors.initials: T
authors.lastname: Tapia
authors.forename: Richard
authors.initials: R
authors.lastname: Ottman
authors.forename: Ratna
authors.initials: R
authors.lastname: Chakrabarti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D017077:Culture Media, Conditioned; D004151:Dipeptides / Q000494:pharmacology; D004792:Enzyme Precursors / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D054461:Lim Kinases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology; D011485:Protein Binding; D021381:Protein Transport; D034622:RNA Interference; D015533:Transcriptional Activation; D022161:Transport Vesicles / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D017077:Culture Media, Conditioned; D004151:Dipeptides; D004792:Enzyme Precursors; D061965:Matrix Metalloproteinase Inhibitors; D008562:Membrane Glycoproteins; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors; C072237:TGOLN2 protein, human; C515892:LIMK1 protein, human; D054461:Lim Kinases; C120487:pro-matrix metalloproteinase 9; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D053511:Matrix Metalloproteinase 14