title: DADS downregulates the Rac1-ROCK1/PAK1-LIMK1-ADF/cofilin signaling pathway,             inhibiting cell migration and invasion.
abstract: The aim of this study was to explore the molecular mechanisms of the diallyl             disulfide (DADS)-mediated downregulation of LIM kinase-1 (LIMK1) and the consequent             inhibition of the migration and invasion of human colorectal cancer cells. RNA             interference technology was used to establish stable LIMK1-miRNA/SW480 cell lines.             The effects of DADS and LIMK1 RNA interference on the migration and invasion of             SW480 cells were observed by scratch wound healing assay and Transwell migration             assay. The effects of DADS on signaling molecules of the Rac1-Rho kinase (ROCK)1/p21-activated             kinase (PAK)1-LIM kinase (LIMK)1-actin depolymerizing factor (ADF)/cofilin pathway             in SW480 cells were examined by RT-PCR and western blot analysis. The healing             and migration rate of the SW480 cells was significantly reduced and the cell penetrating             ability was significantly suppressed (P<0.05) following treatment with DADS             (45 mg/l). The immunohistochemistry and western blot analysis results showed that             DADS significantly downregulated LIMK1 protein expression and suppressed LIMK1             protein phosphorylation. Furthermore, the RT-PCR and western blot analysis results             revealed that DADS suppressed Rac1, ROCK1, PAK1, LIMK1 and destrin mRNA and protein             expression, as well as the protein phosphorylation of LIMK1 and cofilin 1. The             data demonstrate that LIMK1 expression positively correlates with the SW480 cell             migration and invasion ability. DADS downregulates the Rac1-ROCK1/PAK1-LIMK1-ADF/cofilin             signaling pathway, suppressing SW480 cell migration and invasion.
authors.affiliation: Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Cancer Research Institute, University of South China, Hengyang, Hunan 421001, PR China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jian
authors.initials: J
authors.lastname: Su
authors.forename: Ling
authors.initials: L
authors.lastname: Shi
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Liao
authors.forename: Qi
authors.initials: Q
authors.lastname: Su
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D051338:Cofilin 1 / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051345:Destrin / Q000378:metabolism; D004220:Disulfides / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D054461:Lim Kinases / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs; D009361:Neoplasm Invasiveness / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D054462:p21-Activated Kinases / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D000498:Allyl Compounds; D051338:Cofilin 1; C495824:DSTN protein, human; D051345:Destrin; D004220:Disulfides; D035683:MicroRNAs; C107953:RAC1 protein, human; D012333:RNA, Messenger; C028009:diallyl disulfide; C515892:LIMK1 protein, human; D054461:Lim Kinases; C515903:PAK1 protein, human; C515851:ROCK1 protein, human; D054462:p21-Activated Kinases; D054460:rho-Associated Kinases; D020830:rac1 GTP-Binding Protein