Fig. 1.

Schematic of known and putative contributions of emmprin to KSHV-associated cellular pathogenesis. Published data indicate that emmprin mediates critical pathogenic determinants for KSHV-infected cells, including cell migration/invasion, survival, and chemoresistance. Cell invasiveness is mediated through emmprin induction of MMPs and VEGF secretion which is itself dependent upon emmprin stimulation of ERK and Akt, possibly through emmprin-mediated secretion of hyaluronan and hyaluronan interactions with LYVE-1. Emmprin contributes to survival and chemoresistance for KSHV-infected tumor cells through its interactions with LYVE-1 and BCRP and efflux of chemotherapeutic agents. Emmprin stimulation of ERK and Akt may also maintain anti-apoptotic signaling. Whether interactions between emmprin and other known binding partners on the cell surface, including integrins, EP1-4, and MCTs mediate KSHV pathogenesis remains to be determined. Also, it remains unclear whether emmprin is involved in KSHV-induced EndMT through Notch pathways and MT1-MMP. KSHV = Kaposi sarcoma-associated herpesvirus; PGE2 = prostaglandin E2; EP1-4 = prostaglandin E2 receptors; LYVE-1 = lymphatic vessel endothelial hyaluronan receptor-1; BCRP = breast cancer resistance protein; MCT = monocarboxylate transporter; MMP = matrix metalloproteinase; VEGF = vascular endothelial growth factor; MEK = mitogen-activated protein kinase; ERK = extracellular signal-regulated kinase; Endothelial-to-mesenchymal transformation (EndMT); membrane-type-1 matrix metalloproteinase (MT1-MMP).