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Restoration of E-cadherin-based cell–cell adhesion by overexpression of nectin in HSC-39 cells, a human signet ring cell gastric cancer cell line

Oncogene volume 21, pages 4108–4119 (2002)Cite this article

Abstract

Nectin is an immunoglobulin-like adhesion molecule that comprises a family consisting of four members, nectin-1, -2, -3, and -4. Nectin is associated with the actin cytoskeleton through afadin, a nectin- and actin filament-binding protein. The nectin-afadin and cadherin-catenin systems are associated with each other and cooperatively form cell–cell adherens junctions in intact epithelial cells. HSC-39 cells, a human signet ring cell gastric cancer cell line, express E-cadherin but do not form cell–cell adhesion. The β-catenin gene has been shown to be truncated at the N-terminal region including the α-catenin-binding domain in HSC-39 cells, but overexpression of normal β-catenin failed to form cell–cell adhesion. HSC-39 cells expressed nectin-1, -2, and afadin, but not nectin-3. Overexpression of nectin-3 or -2 formed cell–cell adhesion and accumulation of E-cadherin, but not actin filaments, at the cell–cell adhesion sites. Overexpression of a truncated form of nectin-2 incapable of interacting with afadin failed to form cell–cell adhesion. However, the nectin-formed cell–cell adhesion was not so strong as that observed in epithelial cells, such as CaCo-2 cells. Co-expression of nectin-2 and normal β-catenin did not form strong cell–cell adhesion. These results suggest that an unidentified mechanism, by which nectin and E-cadherin form the actin cytoskeleton-associated adherens junctions to form strong cell–cell adhesion, is impaired in HSC-39 cells.

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Acknowledgements

We thank Dr Sh Tsukita (Kyoto University, Kyoto, Japan) for providing us with the mouse β-catenin cDNA and Dr T Imai (KAN Research Institute, Inc., Kyoto, Japan) for Fluorescence-activated cell sorting analysis. The investigation at Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine was supported by grants-in-aid for Scientific Research and for Cancer Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (2001)

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Author notes

  1. Sayumi Shibamoto

    Present address: Department of Molecular Oncology, Genentech, Inc., South San Francisco, 94080-4990, California, USA

  2. Hitoshi Shiozaki

    Present address: First Department of Surgery, Kinki University School of Medicine, Osaka-Sayama, 589-8511, Osaka, Japan

Authors and Affiliations

  1. Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, 565-0871, Japan

    Ying-Feng Peng, Kenji Mandai, Hiroyuki Nakanishi, Wataru Ikeda, Masanori Asada, Yumiko Momose & Yoshimi Takai

  2. Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, 565-0871, Japan

    Hitoshi Shiozaki & Morito Monden

  3. Department of Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, 573-0101, Osaka, Japan

    Sayumi Shibamoto

  4. Central Animal Laboratory, National Cancer Center Research Institute, Tokyo, 104-0045, Japan

    Kazuyoshi Yanagihara

  5. Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Kyoto, 606-8502, Japan

    Masatoshi Takeichi

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Correspondence to Yoshimi Takai.

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Peng, YF., Mandai, K., Nakanishi, H. et al. Restoration of E-cadherin-based cell–cell adhesion by overexpression of nectin in HSC-39 cells, a human signet ring cell gastric cancer cell line. Oncogene 21, 4108–4119 (2002). https://doi.org/10.1038/sj.onc.1205517

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