https://scholars.lib.ntu.edu.tw/handle/123456789/473767
標題: | MDA-9/Syntenin-Slug transcriptional complex promote epithelial-mesenchymal transition and invasion/metastasis in lung adenocarcinoma | 作者: | Wang L.-K. SZU-HUA PAN YIH-LEONG CHANG Hung P.-F. Kao S.-H. Wang W.-L. Lin C.-W. Yang S.-C. Liang C.-H. CHEN-TU WU Hsiao T.-H. Hong T.-M. PAN-CHYR YANG |
公開日期: | 2016 | 出版社: | Impact Journals LLC | 卷: | 7 | 期: | 1 | 起(迄)頁: | 386-401 | 來源出版物: | Oncotarget | 摘要: | Melanoma differentiation-associated gene-9 (MDA-9)/Syntenin is a novel therapeutic target because it plays critical roles in cancer progression and exosome biogenesis. Here we show that Slug, a key epithelial-mesenchymal-transition (EMT) regulator, is a MDA-9/Syntenin downstream target. Mitogen EGF stimulation increases Slug expression and MDA-9/Syntenin nuclear translocation. MDA-9/Syntenin uses its PDZ1 domain to bind with Slug, and this interaction further leads to HDAC1 recruitment, up-regulation of Slug transcriptional repressor activity, enhanced Slug-mediated EMT, and promotion of cancer invasion and metastasis. The PDZ domains and nuclear localization of MDA-9/Syntenin are both required for promoting Slug-mediated cancer invasion. Clinically, patients with high MDA-9/Syntenin and high Slug expressions were associated with poor overall survival compared to those with low expression in lung adenocarcinomas. Our findings provide evidence that MDA-9/Syntenin acts as a pivotal adaptor of Slug and it transcriptionally enhances Slug-mediated EMT to promote cancer invasion and metastasis. ? 2015. Oncotarget. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85001006950&doi=10.18632%2fONCOTARGET.6299&partnerID=40&md5=adaca62aec03d979e82d7004b51e6b25 https://scholars.lib.ntu.edu.tw/handle/123456789/473767 |
ISSN: | 1949-2553 | DOI: | 10.18632/ONCOTARGET.6299 | SDG/關鍵字: | adaptor protein; histone deacetylase 1; MDA 9 protein; mitogenic agent; PDZ1 protein; syntenin; transcription factor; transcription factor Slug; unclassified drug; protein binding; SDCBP protein, human; SNAI1 protein, human; Snai2 protein, mouse; syntenin; transcription factor; transcription factor Snail; adult; animal experiment; animal model; animal tissue; Article; cell nucleus; controlled study; disease association; embryo; epithelial mesenchymal transition; female; human; human cell; lung adenocarcinoma; male; metastasis; mouse; nonhuman; overall survival; protein binding; protein domain; protein expression; protein function; protein localization; protein protein interaction; transcription regulation; tumor invasion; upregulation; adenocarcinoma; animal; confocal microscopy; epithelial mesenchymal transition; gene expression regulation; genetics; HEK293 cell line; immunoblotting; lung tumor; MCF-7 cell line; metabolism; metastasis; nonobese diabetic mouse; pathology; reverse transcription polymerase chain reaction; RNA interference; SCID mouse; survival analysis; tumor cell line; tumor invasion; xenograft; Adenocarcinoma; Animals; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Immunoblotting; Lung Neoplasms; Male; MCF-7 Cells; Mice, Inbred NOD; Mice, SCID; Microscopy, Confocal; Neoplasm Invasiveness; Neoplasm Metastasis; Protein Binding; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Snail Family Transcription Factors; Survival Analysis; Syntenins; Transcription Factors; Transplantation, Heterologous |
顯示於: | 病理學科所 |
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