Kaposi sarcoma-associated herpes virus (KSHV) latent protein LANA modulates cellular genes associated with epithelial-to-mesenchymal transition

Kaposi's sarcoma-associated herpes virus (KSHV) is a gammaherpesvirus associated with Kaposi's sarcoma and various lymphoproliferative diseases. Epithelial-to-mesenchymal transition (EMT) is an important step in the metastasis of cancer cells. Previous studies have shown an important role for EMT markers in B-cell malignancies. In the present study, we investigated the role of the KSHV latent protein LANA in the progression of EMT. Our data suggest that expression of LANA results in an increase in the migration and invasion potential of cancer cells, which is concurrent with modulation of transcriptional regulation and protein expression of several cellular genes associated with EMT. LANA expression results in upregulation of the cellular intermediate filament protein vimentin and transcription factor TCF8/ZEB1 and downregulation of tight junction protein ZO1 and adhesion protein E-cadherin. LANA co-localizes with TCF8/ZEB1, a major contributor in EMT, further suggesting an important role for LANA in epithelial-to-mesenchymal transition of KSHV-infected cancer cells.