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  • Original Paper
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Inactivation of ELF/TGF-β signaling in human gastrointestinal cancer

Oncogene volume 24, pages 8012–8024 (2005)Cite this article

Abstract

TGF-β/Smads regulate a wide variety of biological responses through transcriptional regulation of target genes. ELF, a β-spectrin, plays a key role in the transmission of TGF-β-mediated transcriptional response through Smads. ELF was originally identified as a key protein involved in endodermal stem/progenitor cells committed to foregut lineage. Also, as a major dynamic adaptor and scaffolding protein, ELF is important for the generation of functionally distinct membranes, protein sorting and the development of polarized differentiated epithelial cells. Disruption of elf results in the loss of Smad3/Smad4 activation and, therefore, a disruption of the TGF-β pathway. These observations led us to pursue the function of ELF in gastrointestinal (GI) epithelial cell–cell adhesion and tumor suppression. Here, we show a significant loss of ELF and reduced Smad4 expression in human gastric cancer tissue samples. Also, of the six human gastric cancer cell lines examined, three show deficient ELF expression. Furthermore, we demonstrate the rescue of E-cadherin-dependent homophilic cell–cell adhesion by ectopic expression of full-length elf. Our results suggest that ELF has an essential role in tumor suppression in GI cancers.

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Acknowledgements

We thank Dr M Zasloff, Dr R Schlegel, Tiffany Blake and Amanda Elson for critical review of the manuscript. The study was supported by NIHRO1 DK56111 (LM), NIHRO1 DK58637 (BM), VA Merit Award (LM) and R Robert and Sally D Funderburg Research Scholar (LM).

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Author notes

  1. 8 Katuri Varalakshmi and Tang Yi contributed equally to this work

Authors and Affiliations

  1. Department of Surgical Sciences, Laboratory of Developmental Molecular Biology, Medicine, Lombardi Cancer Center, Georgetown University, Washington, 20007, DC, USA

    Varalakshmi Katuri, Yi Tang, Wilma Jogunoori, Eugene A Volpe, Lopa Mishra & Bibhuti Mishra

  2. Department of Veterans Affairs Medical Center, 50 Irving Street, NW, Washington, 20007, DC, USA

    Wilma Jogunoori, Anton N Sidawy & Lopa Mishra

  3. Departments of Surgery, Georgetown University, Washington, 20007, DC, USA

    Blair Marshall, Eugene A Volpe, Stephen Evans & Bibhuti Mishra

  4. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, 77030, TX, USA

    Asif Rashid

  5. Department of Pharmacology, Dalhousie University, B3H 4R2, Halifax, Nova Scotia, Canada

    Jonathan Blay

  6. Departments of Cell Biology, Georgetown University, Washington, 20007, DC, USA

    G Ian Gallicano

  7. Fels Institute for Cancer Research and Molecular Biology, 3307 North Broad Street, Philidelphia, 19140, PA, USA

    E Premkumar Reddy

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Katuri, V., Tang, Y., Marshall, B. et al. Inactivation of ELF/TGF-β signaling in human gastrointestinal cancer. Oncogene 24, 8012–8024 (2005). https://doi.org/10.1038/sj.onc.1208946

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  • DOI: https://doi.org/10.1038/sj.onc.1208946

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