title: The tumor marker Fascin is strongly induced by the Tax oncoprotein of HTLV-1 through NF-kappaB signals.
abstract: Oncogenic transformation of CD4(+) T cells by human T-cell lymphotropic virus type 1 (HTLV-1) is understood as the initial step to adult T-cell leukemia/lymphoma, a process that is mainly initiated by perturbation of cellular signaling by the viral Tax oncoprotein, a potent transcriptional regulator. In search of novel biomarkers with relevance to oncogenesis, we identified the tumor marker and actin-bundling protein Fascin (FSCN1) to be specifically and strongly up-regulated in both HTLV-1-transformed and adult T-cell leukemia/lymphoma 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 was sufficient to induce high levels of Fascin. Nuclear factor-κB signals were important for Tax-mediated transcriptional regulation of Fascin in T cells. This suggests that Fascin up-regulation by Tax contributes to the development of HTLV-1-associated pathogenesis.
authors.affiliation: Institute of Clinical and Molecular Virology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schlossgarten 4, Erlangen, Germany. andrea.kress@viro.med.uni-erlangen.de
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Kress
authors.forename: Martina
authors.initials: M
authors.lastname: Kalmer
authors.forename: Aileen G
authors.initials: AG
authors.lastname: Rowan
authors.forename: Ralph
authors.initials: R
authors.lastname: Grassmann
authors.forename: Bernhard
authors.initials: B
authors.lastname: Fleckenstein
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000502:physiology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D016356:Gene Products, tax / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology; D046228:Microarray Analysis; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D016356:Gene Products, tax; D008840:Microfilament Proteins; D016328:NF-kappa B; D034741:RNA, Small Interfering; C514970:tax protein, Human T-lymphotrophic virus 1; C020324:fascin