NAMPT inhibition results in apoptosis of activated T lymphocytes: evidence for a role of PARP1

Boosting NAD + biosynthesis with NAD + intermediates has been proposed as a strategy for preventing and treating age-associated diseases, including cancer. However, concerns in this area were raised by observations that nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in mammalian NAD + biosynthesis, is frequently up-regulated in human malignancies, including breast cancer, suggesting possible pro-tumorigenic effects for this protein. We addressed this issue by studying NAMPT expression and function in human breast cancer in vivo and in vitro. Our data indicates that high NAMPT levels are associated with aggressive pathological and molecular features, such as ER negativity, as well as Her2-enriched and basal-like PAM50 phenotypes. Consistent with these findings, we http://www.jbc.org/cgi/doi/10.1074/jbc.M114.594721 The latest version is at JBC Papers in Press. Published on October 20, 2014 as Manuscript M114.594721 Copyright 2014 by The American Society for Biochemistry and Molecular Biology, Inc. by gest on N ovem er 9, 2017 hp://w w w .jb.org/ D ow nladed from