Laforin confers cancer resistance to energy deprivation-induced apoptosis.
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.
Division of Immunotherapy, Section of General Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
Yin
Y
Wang
Yan
Y
Liu
Cindy
C
Wu
Beth
B
McNally
Yang
Y
Liu
Pan
P
Zheng
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001483:Base Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D003847:Deoxyglucose / Q000494:pharmacology; D004734:Energy Metabolism; D006801:Humans; D008223:Lymphoma / Q000235:genetics / Q000473:pathology; D051379:Mice; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering
D034741:RNA, Small Interfering; D003847:Deoxyglucose; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C114990:EPM2A protein, human