S-Space College of Medicine/School of Medicine (의과대학/대학원) Program in Cancer Biology (협동과정-종양생물학전공) Journal Papers (저널논문_협동과정-종양생물학전공)
TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition
- 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
- Nature Publishing Group
- Oncogene. 2008 Apr 17;27(18):2635-47. Epub 2007 Oct 29.
- Animals; Cadherins/antagonists & inhibitors/genetics/metabolism; Cell Adhesion; Cell Communication/drug effects/genetics; Cell Line, Tumor; Cell Movement/drug effects/genetics; Epithelial Cells/*enzymology/pathology; Gastrointestinal Neoplasms/*enzymology/genetics/pathology/therapy; *Gene Expression Regulation, Enzymologic/drug effects/genetics; *Gene Expression Regulation, Neoplastic/drug effects/genetics; Humans; Liver Neoplasms/enzymology/genetics/pathology/secondary/therapy; Lung Neoplasms/*enzymology/genetics/pathology/therapy; Membrane Proteins/antagonists & inhibitors/*biosynthesis/genetics; Mice; Mice, Nude; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins/antagonists & inhibitors/*biosynthesis/genetics; Neoplasm Transplantation; Nerve Tissue Proteins/genetics/metabolism; RNA, Small Interfering/genetics; RNA-Binding Proteins/genetics/metabolism; Serine Endopeptidases/*biosynthesis/genetics; Tumor Markers, Biological/*biosynthesis/genetics
- 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.
- 1476-5594 (Electronic)
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