KSHV (Kaposi's sarcoma-associated herpesvirus), or HHV-8 (human herpesvirus 8), is associated with the pathogenesis of KS, the most common AIDS-related malignancy. xCT (functional subunit of the cystine/glutamate transporter xc- system) is known as the HHV-8 fusion-entry receptor as well as an oncogenic protein. How the xCT triggers the signal transduction of HHV-8 infection and the cell proliferation remains incomplete. We found that xCT was overexpressed in KS tissues and HHV-8-positive BCBL-1 cells. When xCT cDNA plasmids were transfected into the HHV-8-negative BJAB cells, the expression of 14-3-3beta and cell growth rate were increased. In contrast, the expression of 14-3-3beta and the cell growth rate of HHV-8-positive BCBL-1 cells were suppressed by either xCT siRNA (short interfering RNA) or an xCT inhibitor, sulfsalazine. These results suggest that 14-3-3beta is a downstream effector of xCT in KS to mediate the cell proliferation.