Epstein-Barr virus latent membrane protein 1 increases chemo-resistance of cancer cells via cytoplasmic sequestration of Pim-1

Abstract

Improved treatment of EBV positive lymphoma depends on the identification of molecular mechanism underlying chemo-resistance. LMP1 is an essential transmembrane protein for EBV-induced immortalization of hematopoietic cells. Herein, we show that an oncogenic Pim-1 is translocated to the cytoplasm by LMP1. Three lines of evidence indicate that cytoplasmic sequestration of Pim-1 may be required for LMP1-induced cancer cell survival. First, Pim-1 enhanced the survival of LMP1-overexpressing cells treated with doxorubicin. Second, nuclear export of Pim-1 was sufficient to increase the survival. Third, knockdown of Pim-1 effectively suppressed LMP-1-induced survival of cancer cells. Collectively, these data suggest that Pim-1 is a downstream target of LMP1, and that it contributes to the chemo-resistance of cancer cells. © 2010 Elsevier Inc.