Huang F.Chen Y.Chang C.RAY-HWANG YUANYUNG-MING JENG2020-03-062020-03-0620120143-3334https://www.scopus.com/inward/record.uri?eid=2-s2.0-84864320039&doi=10.1093%2fcarcin%2fbgs131&partnerID=40&md5=0bcdb0202b64df5fa56e8ec6bc6ac4c3https://scholars.lib.ntu.edu.tw/handle/123456789/473376Hepatocyte growth factor (HGF) is a secretory protein that plays important roles in cancer growth and metastasis. Lymphoid-enhancing factor 1 (LEF1) is a transcription factor mediating Wnt/β-catenin signaling. Using microarray analysis, we found HGF induced expression of LEF1 in liver and breast cancer cell lines. HGF induced expression of LEF1 through phosphatidylinositol 3-kinase/Akt and nuclear factor-kappa B (NF-κB) signaling. Multiple NF-κB-binding sites were mapped within 3 kb upstream of LEF1 transcription initiation site. NF-κB binding to a site 2 kb upstream of LEF1 transcription initiation site was confirmed by chromatin immunoprecipitation assay. Knockdown of LEF1 inhibited the expression of Slug and Zinc finger E-box-binding homeobox 2 (ZEB2) and markedly attenuated HGF-induced tumor migration and invasion. Using immunohistochemical staining, we found LEF1 was frequently expressed in multiple types of carcinoma but not in the non-tumorous epithelial cells. Our finding suggest that transcriptional activation of LEF1 is a mechanism of cross talk between HGF/c-Met and Wnt/β-catenin pathways and is essential for HGF-induced tumor invasion. ? The Author 2012. Published by Oxford University Press. All rights reserved.[SDGs]SDG3beta catenin; homeodomain protein; immunoglobulin enhancer binding protein; lymphoid enhancer factor 1; mitogen activated protein kinase; phosphatidylinositol 3 kinase; protein kinase B; scatter factor; transcription factor Slug; unclassified drug; Wnt protein; zinc finger E box binding homeobox 2 protein; article; binding site; breast cancer; cancer cell culture; cancer invasion; cell migration; chromatin immunoprecipitation; controlled study; epithelial mesenchymal transition; fibroblast; gene overexpression; gene silencing; immunohistochemistry; liver cancer; microarray analysis; priority journal; transcription initiation; Wnt signaling pathway; beta Catenin; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Female; HEK293 Cells; Hep G2 Cells; Hepatocyte Growth Factor; Homeodomain Proteins; Humans; Liver Neoplasms; Lymphoid Enhancer-Binding Factor 1; Neoplasm Invasiveness; NF-kappa B; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-met; Repressor Proteins; RNA Interference; RNA, Small Interfering; Signal Transduction; Transcription Factors; Transcriptional Activation; Wnt Signaling Pathwayjournal article10.1093/carcin/bgs131224366132-s2.0-84864320039