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Transforming Growth Factor-β in Cancer Therapy, Volume I pp 91–103Cite as

Interaction of Smad4 and Embryonic Liver Fodrin-β-spectrin in Hyperplasia, Neoplasia, and Tumor Suppression

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Transforming growth factor (TGF)-β is both a suppressor and promoter of tumorigenesis; however, its contribution to early tumor suppression and staging remains largely unknown. In search of the mechanism of early tumor suppression, we focus on Smad4, a transducer of TGF-β signaling, and embryonic liver fodrin (ELF), a β-spectrin, in tumorigenesis by linking a major, dynamic scaffolding protein and a key signaling protein. ELF activates and modulates Smad4 activation of the TGF-β response to confer cell polarity, to maintain cell architecture, and to inhibit epithelial-to-mesenchymal transition. In human gastric tumor samples, a significant loss of ELF and reduction of Smad4 expression was recently found. An examination of elf +/−, Smad4+/−, and elf +/−/Smad4+/− mice revealed that disruption of ELF and Smad4 displayed a synergistic effect on tumor formation in terms of incidence and duration, suggesting a cooperative interaction between ELF and Smad4 leading to enhanced tumor suppression. This review examines our understanding of the significance of the interactions between ELF and Smad4, through regulation of the TGF-β signaling pathway and repression of tumor formation.

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Authors and Affiliations

  1. Radiation Medicine Branch, National Cancer Center, Goyang, Gyeonggi, Korea

    Sang Soo Kim PhD

  2. Department of Surgery, VA Medical Center, Washington, DC, USA

    Charles Shuman MD & Lopa Mishra MD

  3. Departments of Medicine and Surgery, Lombardi Cancer Center, Georgetown University, Washington, DC, USA

    Lopa Mishra MD

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Kim, S.S., Shuman, C., Mishra, L. (2008). Interaction of Smad4 and Embryonic Liver Fodrin-β-spectrin in Hyperplasia, Neoplasia, and Tumor Suppression. In: Transforming Growth Factor-β in Cancer Therapy, Volume I. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-292-2_6

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  • DOI: https://doi.org/10.1007/978-1-59745-292-2_6

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