Laforin confers cancer resistance to energy deprivation-induced apoptosis

Abstract

A long-standing but poorly understood observation in experimental cancer therapy is the heterogeneity in cancer susceptibility to energy deprivation. Here, we show that the hexose kinase inhibitor 2-deoxyglucose (2-dG) preferentially kills cancer cells with defective laforin expression and significantly increases the survival of mice with aggressive lymphoma due to a genetic defect of the laforin-encoding Epm2a gene. Normal cells from Epm2a -/- mice also had greatly increased susceptibility to 2-dG. Thus, laforin is a novel regulator for cellular response to energy deprivation and its defects in cancer cells may be targeted for cancer therapy. ©2008 American Association for Cancer Research.