Kaposi's Sarcoma (KS) is the most common tumor in AIDs patients and is currently the most commonly reported tumor in regions of Africa. KS tumors can spontaneously regress and KS tumor cells rarely grow out as transformed cells indicating that KS tumors are hyperplasias caused by stimulation of the tumor cell. Kaposi's Sarcoma-associated herpesvirus (KSHV) is an essential etiologic agent for KS. In KS, KSHV is found in the main KS tumor cell, the spindle cell, a cell of endothelial origin. In the KS tumor KSHV is predominantly latent where its limited gene expression leads to many changes in the host cell. KSHV alteration of host signaling pathways common to many types of tumors may be critical for the maintenance of the hyperplasia. Persistent signaling of STAT3 is common in many tumors and is induced by latent KSHV infection of endothelial cells. Most tumors alter the source of their metabolism from oxidative phosphorylation to glycolysis through activation of Hypoxia induced factors. KSHV also activates hypoxia induced factors in endothelial cells. KSHV persistent activation of signaling pathways like STAT3 and the Hypoxia response pathway are likely to play an important role in KS tumorigenesis and might provide important therapeutic targets for KS.
Kaposi's Sarcoma (KS) is the most widespread tumor of AIDS patients and is the most commonly reported tumor in regions of Africa. Kaposi's Sarcoma-associated herpesvirus (KSHV) is an essential agent for the formation of KS. This proposal aims to gain a further understanding of how KSHV alters host cell signaling to induce KS tumors. These pathways may provide therapeutic targets for KS tumor therapy.
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