RRC ID 63902
著者 Kudo K, Nomura M, Sakamoto Y, Ito S, Morita M, Kawai M, Yamashita Y, Ito K, Yamada H, Shima H, Yaegashi N, Tanuma N.
タイトル Divergent metabolic responses dictate vulnerability to NAMPT inhibition in ovarian cancer.
ジャーナル FEBS Lett
Abstract It is of current interest to target cancer metabolism as treatment for many malignancies, including ovarian cancer (OVC), in which few druggable driver mutations have been identified. Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in the NAD salvage pathway, is a potential therapeutic target in OVC. However, factors that determine responsiveness to NAMPT inhibition are not fully understood. Here, we report that OVC cell lines can be divided into subgroups exhibiting NAMPT-dependent or NAMPT-independent glycolysis, and these metabolic differences correlate with vulnerability to NAMPT inhibition. Interestingly, cells showing NAMPT-dependent glycolysis were enriched in a group of cells lacking BRCA1/2 gene mutations. Our findings suggest the importance of selecting appropriate patients for NAMPT-targeting therapy in OVC.
巻・号 594(9)
ページ 1379-1388
公開日 2020-5-1
DOI 10.1002/1873-3468.13736
PMID 31950503
MeSH Acrylamides / pharmacology Cell Line, Tumor Cytokines / antagonists & inhibitors* Cytokines / metabolism* Female Glycolysis / drug effects Humans Lactic Acid / metabolism NAD / metabolism Niacin / metabolism Nicotinamide Phosphoribosyltransferase / antagonists & inhibitors* Nicotinamide Phosphoribosyltransferase / metabolism* Ovarian Neoplasms / drug therapy* Ovarian Neoplasms / genetics Ovarian Neoplasms / metabolism* Ovarian Neoplasms / pathology Piperidines / pharmacology Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
IF 3.057
リソース情報
ヒト・動物細胞 JHOS-2(RCB1521) JHOS-4(RCB1678)