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Retrovirology

, 8:A186 | Cite as

The tumour marker Fascin is strongly induced by Tax of HTLV-1 through NF-κB signals in T lymphocytes

  • Andrea K Kress
  • Martina Kalmer
  • Aileen G Rowan
  • Ralph Grassmann
  • Bernhard Fleckenstein
Open Access
Meeting abstract
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Keywords

Transcriptional Regulation Tumour Marker Direct Link Jurkat Cell Strong Decrease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

In search of novel biomarkers of HTLV-1- transformed cells with relevance to oncogenesis, we identified the tumour marker and actin-bundling protein Fascin (FSCN1) to be specifically and strongly upregulated in both HTLV-1-transformed and ATLL-patient-derived CD4+ T cells. Fascin is important for migration and metastasis in various types of cancer. Here we report that a direct link can exist between a single viral oncoprotein and Fascin expression, as the viral oncoprotein Tax of HTLV-1 was sufficient to induce high levels of Fascin. In contrast, Tax-2 of HTLV-2 could not induce Fascin. Expression of Fascin was also detectable in primary CD4+ T cells of ATLL-patients after they expressed Tax spontaneously. Immunofluorescence analysis revealed that Fascin could colocalize with Actin in the cytoplasm and at the membrane of HTLV-1-transformed cells. We found a novel mode of transcriptional regulation of Fascin by showing the importance of NF-κB signals for Tax-mediated induction of Fascin in T cells. Chemical and dominant-negative inhibition of the NF-κB pathway as well as a NF-κB-deficient Tax-mutant led to a strong decrease of Fascin mRNA and protein in Tax-transfected Jurkat cells. Additionally, in HTLV-1-/Tax-transformed cells Fascin transcripts were strongly reduced after chemical inhibition of IκB-kinase. Knockdown of Fascin by lentiviral transduction of shRNA decreased the invasive capacity of ATLL-derived cells into extracellular matrix. Thus, we have clearly shown that the tumour marker Fascin can be induced by the viral Tax oncoprotein through NF-κB signals. Our data suggest that Fascin up-regulation by Tax contributes to the development of HTLV-1-associated pathogenesis.

Copyright information

© Kress et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Authors and Affiliations

  • Andrea K Kress
    • 1
  • Martina Kalmer
    • 1
  • Aileen G Rowan
    • 2
  • Ralph Grassmann
    • 1
  • Bernhard Fleckenstein
    • 1
  1. 1.Institute of Clinical and Molecular VirologyFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany
  2. 2.Department of ImmunologyWright-Fleming Institute, Imperial CollegeLondonUK

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