RRC ID 37478
著者 Douchi D, Ohtsuka H, Ariake K, Masuda K, Kawasaki S, Kawaguchi K, Fukase K, Oikawa M, Motoi F, Naitoh T, Katayose Y, Egawa S, Unno M.
タイトル Silencing of LRRFIP1 reverses the epithelial-mesenchymal transition via inhibition of the Wnt/β-catenin signaling pathway.
ジャーナル Cancer Lett
Abstract The canonical Wnt/β-catenin signaling pathway has been shown to promote the epithelial-mesenchymal transition (EMT), which is a crucial process in multiple embryonic developmental processes and the progression of carcinomas. We recently provided evidence that leucine-rich repeat flightless-1-interacting protein 1 (LRRFIP1) promotes cancer metastasis and invasion. In the present study, we identified the signaling elements targeted by LRRFIP1 for promotion of the EMT in pancreatic and lung cancer. LRRFIP1 silencing reversed the EMT, as shown by increased expression of E-cadherin (an epithelial marker) and decreased expression of vimentin (a mesenchymal marker). Silencing of LRRFIP1 up-regulated phosphorylation of β-catenin and decreased its nuclear localization by targeting the β-catenin destruction complex. The expression of β-catenin and E-cadherin in the plasma membrane fraction was increased in LRRFIP1 silenced cancer cells, and the migration and invasion capabilities were strongly inhibited. In addition, this protein was highly expressed at the invasion front of malignant tissue collected from pancreatic cancer patients. Consequently, our data strongly suggested that LRRFIP1 played an important role in the invasion of carcinoma cells. Our data provide experimental evidence that LRRFIP1 is an attractive candidate for targeted therapy in human cancers.
巻・号 365(1)
ページ 132-40
公開日 2015-8-28
DOI 10.1016/j.canlet.2015.05.023
PII S0304-3835(15)00373-0
PMID 26047573
MeSH Active Transport, Cell Nucleus Antigens, CD Cadherins / genetics Cadherins / metabolism Cell Line, Tumor Cell Movement Cell Proliferation Epithelial-Mesenchymal Transition* Gene Expression Regulation, Neoplastic Humans Lung Neoplasms / genetics Lung Neoplasms / metabolism* Lung Neoplasms / pathology Neoplasm Invasiveness Pancreatic Neoplasms / genetics Pancreatic Neoplasms / metabolism* Pancreatic Neoplasms / pathology Phosphorylation Promoter Regions, Genetic RNA Interference* RNA-Binding Proteins / genetics RNA-Binding Proteins / metabolism* Transfection Wnt Signaling Pathway* beta Catenin / metabolism*
IF 7.36
引用数 23
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 PANC-1(RCB2095)