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

Oncogene volume 27, pages 2635–2647 (2008)Cite this article

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.

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Author notes

  1. H Jung and K P Lee: These authors contributed equally to this work.

Authors and Affiliations

  1. Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejon, Korea

    H Jung, K P Lee, S J Park, J H Park, Y-s Jang, S-Y Choi, J-G Jung, K Jo, H J Hong, S Kim & Y W Park

  2. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejon, Korea

    K P Lee & D-S Lim

  3. Digital Genomics, Inc., Seoul, Korea

    D Y Park & J H Yoon

  4. Department of Thoracic Surgery, Korea Cancer Center Hospital, Seoul, Korea

    J-H Park

  5. Department of Surgery, Chonnam National University Medical School, Hwasun, Korea

    G-R Hong & Y-K Park

  6. Department of Pathology, Chonnam National University Medical School, Hwasun, Korea

    C Choi

  7. Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea

    J W Lee

  8. Department of Tumor Biology, College of Medicine, Seoul National University, Seoul, Korea

    J W Lee

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  1. H Jung
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Correspondence to S Kim.

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Jung, H., Lee, K., Park, S. et al. TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial–mesenchymal transition. Oncogene 27, 2635–2647 (2008). https://doi.org/10.1038/sj.onc.1210914

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  • DOI: https://doi.org/10.1038/sj.onc.1210914

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