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

• Published in: Oncogene Vol. 27; no. 18; pp. 2635 - 2647
• Main 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.04.2008; Nature Publishing; Nature Publishing Group
• Subjects: Actin; Animals; Apoptosis; Biological and medical sciences; Biomarkers, Tumor - biosynthesis; Biomarkers, Tumor - genetics; Cadherins - antagonists & inhibitors; Cadherins - genetics; Cadherins - metabolism; Cancer; Cancer cells; Care and treatment; Cell Adhesion; Cell Biology; Cell Communication - drug effects; Cell Communication - genetics; Cell Line, Tumor; Cell Movement - drug effects; Cell Movement - genetics; Cell physiology; Cell proliferation; Cell surface; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cellular biology; Colon; Colon cancer; Colorectal cancer; Control; E-cadherin; Epithelial Cells - enzymology; Epithelial Cells - pathology; Fundamental and applied biological sciences. Psychology; Gastric cancer; Gastrointestinal Neoplasms - enzymology; Gastrointestinal Neoplasms - genetics; Gastrointestinal Neoplasms - pathology; Gastrointestinal Neoplasms - therapy; Gene Expression Regulation, Enzymologic - drug effects; Gene Expression Regulation, Enzymologic - genetics; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - genetics; Genetic aspects; Genetics; Human Genetics; Humans; Internal Medicine; Invasiveness; Liver Neoplasms - enzymology; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Liver Neoplasms - secondary; Liver Neoplasms - therapy; Lung cancer; Lung Neoplasms - enzymology; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Medicine; Medicine & Public Health; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - biosynthesis; Membrane Proteins - genetics; Mesenchyme; Metastases; Metastasis; Mice; Mice, Nude; Molecular and cellular biology; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Neoplasm Transplantation; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Oncology; original-article; Pancreatic cancer; Physiological aspects; Proteases; Reverse transcription; Risk factors; RNA, Small Interfering - genetics; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Serine Endopeptidases - biosynthesis; Serine Endopeptidases - genetics; Serine proteinase; siRNA; Therapeutic targets; Tumor cell lines; Tumor cells; South Korea; invasion; serine protease; metastasis; E-cadherin; EMT; TMPRSS4; Human; Enzyme; Migration; Serine; Mesenchyma; Malignant tumor; Metastasis; Epithelium; Carcinogenesis; Peptidases; Hydrolases; E Cadherin; Tumor cell; Cancer
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1210914

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.