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EPLIN downregulation promotes epithelial–mesenchymal transition in prostate cancer cells and correlates with clinical lymph node metastasis

Oncogene volume 30, pages 4941–4952 (2011)Cite this article

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Abstract

Epithelial–mesenchymal transition (EMT) is a crucial mechanism for the acquisition of migratory and invasive capabilities by epithelial cancer cells. By conducting quantitative proteomics in experimental models of human prostate cancer (PCa) metastasis, we observed strikingly decreased expression of EPLIN (epithelial protein lost in neoplasm; or LIM domain and actin binding 1, LIMA-1) upon EMT. Biochemical and functional analyses demonstrated that EPLIN is a negative regulator of EMT and invasiveness in PCa cells. EPLIN depletion resulted in the disassembly of adherens junctions, structurally distinct actin remodeling and activation of β-catenin signaling. Microarray expression analysis identified a subset of putative EPLIN target genes associated with EMT, invasion and metastasis. By immunohistochemistry, EPLIN downregulation was also demonstrated in lymph node metastases of human solid tumors including PCa, breast cancer, colorectal cancer and squamous cell carcinoma of the head and neck. This study reveals a novel molecular mechanism for converting cancer cells into a highly invasive and malignant form, and has important implications in prognosis and treating metastasis at early stages.

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Acknowledgements

We thank Dr Jin-Tang Dong for critical reading of the manuscript, and Dr Anthea Hammond for editorial assistance. This work was supported by the Department of Defense PC060566, American Cancer Society RSG-10-140-01, Georgia Cancer Coalition Cancer Research Award, Kennedy Seed Grant, Emory University Research Committee Award, Winship MPB Seed Grant (DW), National Cancer Institute grants P01 CA98912, R01 CA122602 and Department of Defense PC060866 (LWKC), Georgia Cancer Coalition Distinguished Scholar Grant (OK) and National Cancer Institute grant 1R43CA141870 (YAW).

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Authors and Affiliations

  1. Department of Urology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA

    S Zhang, A O Osunkoya, S Iqbal, Y Wang, F F Marshall, O Kucuk & D Wu

  2. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA

    X Wang, Z Chen, D M Shin & O Kucuk

  3. Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA

    A O Osunkoya & S Müller

  4. Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA

    Z Chen

  5. Department of Medicine, Uro-Oncology Research Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    S Josson, R Wang, L W K Chung & H E Zhau

  6. Division of Human Biology, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA

    I M Coleman & P S Nelson

  7. Ocean NanoTech, LLC, Springdale, AR, USA

    Y A Wang

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Zhang, S., Wang, X., Osunkoya, A. et al. EPLIN downregulation promotes epithelial–mesenchymal transition in prostate cancer cells and correlates with clinical lymph node metastasis. Oncogene 30, 4941–4952 (2011). https://doi.org/10.1038/onc.2011.199

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  • DOI: https://doi.org/10.1038/onc.2011.199

Keywords

  • EPLIN
  • epithelial–mesenchymal transition
  • prostate cancer
  • lymph node metastasis
  • cytoskeleton

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