CIIA induces the epithelial-mesenchymal transition and cell invasion.
Epithelial-mesenchymal transition (EMT) and the acquisition of invasive potential are key events in tumor progression. We now show that CIIA, originally identified as an anti-apoptotic protein, induces the EMT and promotes cell migration and invasion. Ectopic expression of CIIA induced down-regulation of E-cadherin and claudin-1 as well as up-regulation of N-cadherin in MDCK cells. It also disrupted the differentiated epithelial morphology of MDCK cells grown in three-dimensional Matrigel cultures as well as increased the migration and invasion of MDCK cells in vitro. Furthermore, depletion of endogenous CIIA by RNA interference inhibited the migration and invasion of HeLa cells, and this inhibition was abolished by RNA interference-mediated depletion of claudin-1. These results suggest that CIIA functions as an inducer of cell invasion, and this effect is mediated, at least in part, through down-regulation of claudin-1.
Han
Sun-Young
SY
Pharmacology Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
Hwang
Hyun Sub
HS
Chae
Ji Soo
JS
Yang
Suk-Jin
SJ
Yoon
Je-Hyun
JH
Yeom
Young Il
YI
Choi
Eui-Ju
EJ
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement; D004285:Dogs; D004848:Epithelium / Q000378:metabolism / Q000473:pathology*; D006367:HeLa Cells; D006801:Humans; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness
D051017:Apoptosis Regulatory Proteins; C109664:caspase-activated DNase inhibitor