https://scholars.lib.ntu.edu.tw/handle/123456789/473376
標題: | Hepatocyte growth factor activates Wnt pathway by transcriptional activation of LEF1 to facilitate tumor invasion | 作者: | Huang F. Chen Y. Chang C. RAY-HWANG YUAN YUNG-MING JENG |
公開日期: | 2012 | 卷: | 33 | 期: | 6 | 起(迄)頁: | 1142-1148 | 來源出版物: | Carcinogenesis | 摘要: | Hepatocyte 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. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84864320039&doi=10.1093%2fcarcin%2fbgs131&partnerID=40&md5=0bcdb0202b64df5fa56e8ec6bc6ac4c3 https://scholars.lib.ntu.edu.tw/handle/123456789/473376 |
ISSN: | 0143-3334 | DOI: | 10.1093/carcin/bgs131 | SDG/關鍵字: | beta 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 Pathway |
顯示於: | 病理學科所 |
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