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TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition

Cited 106 time in Web of Science Cited 113 time in Scopus
Authors
Jung, H; Lee, K P; Park, S J; Park, J H; Jang, Y-S; Choi, S-Y; Jung, J-G; Jo, K; Park, D Y; Yoon, J H; Park, J-H; Lim, D-S; Hong, G-R; Choi, C; Park, Y-K; Lee, J W; Hong, H J; Kim, S; Park, Y W
Issue Date
2007-10-31
Publisher
Nature Publishing Group
Citation
Oncogene. 2008 Apr 17;27(18):2635-47. Epub 2007 Oct 29.
Keywords
AnimalsCadherins/antagonists & inhibitors/genetics/metabolismCell AdhesionCell Communication/drug effects/geneticsCell Line, TumorCell Movement/drug effects/geneticsEpithelial Cells/*enzymology/pathologyGastrointestinal Neoplasms/*enzymology/genetics/pathology/therapy*Gene Expression Regulation, Enzymologic/drug effects/genetics*Gene Expression Regulation, Neoplastic/drug effects/geneticsHumansLiver Neoplasms/enzymology/genetics/pathology/secondary/therapyLung Neoplasms/*enzymology/genetics/pathology/therapyMembrane Proteins/antagonists & inhibitors/*biosynthesis/geneticsMiceMice, NudeNeoplasm InvasivenessNeoplasm MetastasisNeoplasm Proteins/antagonists & inhibitors/*biosynthesis/geneticsNeoplasm TransplantationNerve Tissue Proteins/genetics/metabolismRNA, Small Interfering/geneticsRNA-Binding Proteins/genetics/metabolismSerine Endopeptidases/*biosynthesis/geneticsTumor Markers, Biological/*biosynthesis/genetics
Abstract
TMPRSS4 is a novel type II transmembrane serine protease found at the cell surface that is highly expressed in pancreatic, colon and gastric cancer tissues. However, the biological functions of TMPRSS4 in cancer are unknown. Here we show, using reverse transcription-PCR, that TMPRSS4 is highly elevated in lung cancer tissues compared with normal tissues and is also broadly expressed in a variety of human cancer cell lines. Knockdown of TMPRSS4 by small interfering RNA treatment in lung and colon cancer cell lines was associated with reduction of cell invasion and cell-matrix adhesion as well as modulation of cell proliferation. Conversely, the invasiveness, motility and adhesiveness of SW480 colon carcinoma cells were significantly enhanced by TMPRSS4 overexpression. Furthermore, overexpression of TMPRSS4 induced loss of E-cadherin-mediated cell-cell adhesion, concomitant with the induction of SIP1/ZEB2, an E-cadherin transcriptional repressor, and led to epithelial-mesenchymal transition events, including morphological changes, actin reorganization and upregulation of mesenchymal markers. TMPRSS4-overexpressing cells also displayed markedly increased metastasis to the liver in nude mice upon intrasplenic injection. Taken together, these studies suggest that TMPRSS4 controls the invasive and metastatic potential of human cancer cells by facilitating an epithelial-mesenchymal transition; TMPRSS4 may be a potential therapeutic target for cancer treatment.
ISSN
1476-5594 (Electronic)
Language
English
URI
http://www.nature.com/onc/journal/v27/n18/abs/1210914a.html

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17968309

http://hdl.handle.net/10371/29537
DOI
https://doi.org/10.1038/sj.onc.1210914
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College of Medicine/School of Medicine (의과대학/대학원)Program in Cancer Biology (협동과정-종양생물학전공)Journal Papers (저널논문_협동과정-종양생물학전공)
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