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.
Wang
Yin
Y
Division of Immunotherapy, Section of General Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
Liu
Yan
Y
Wu
Cindy
C
McNally
Beth
B
Liu
Yang
Y
Zheng
Pan
P
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