論文 - 詳細
| RRC ID | 77612 |
|---|---|
| 著者 | Nomura M, Ohuchi M, Sakamoto Y, Kudo K, Yaku K, Soga T, Sugiura Y, Morita M, Hayashi K, Miyahara S, Sato T, Yamashita Y, Ito S, Kikuchi N, Sato I, Saito R, Yaegashi N, Fukuhara T, Yamada H, Shima H, Nakayama KI, Hirao A, Kawasaki K, Arai Y, Akamatsu S, Tanuma SI, Sato T, Nakagawa T, Tanuma N. |
| タイトル | Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma. |
| ジャーナル | Nat Commun |
| Abstract |
Nicotinamide phosphoribosyltransferase (NAMPT) plays a major role in NAD biosynthesis in many cancers and is an attractive potential cancer target. However, factors dictating therapeutic efficacy of NAMPT inhibitors (NAMPTi) are unclear. We report that neuroendocrine phenotypes predict lung and prostate carcinoma vulnerability to NAMPTi, and that NAMPTi therapy against those cancers is enhanced by dietary modification. Neuroendocrine differentiation of tumor cells is associated with down-regulation of genes relevant to quinolinate phosphoribosyltransferase-dependent de novo NAD synthesis, promoting NAMPTi susceptibility in vitro. We also report that circulating nicotinic acid riboside (NAR), a non-canonical niacin absent in culture media, antagonizes NAMPTi efficacy as it fuels NAMPT-independent but nicotinamide riboside kinase 1-dependent NAD synthesis in tumors. In mouse transplantation models, depleting blood NAR by nutritional or genetic manipulations is synthetic lethal to tumors when combined with NAMPTi. Our findings provide a rationale for simultaneous targeting of NAR metabolism and NAMPT therapeutically in neuroendocrine carcinoma. |
| 巻・号 | 14(1) |
| ページ | 8095 |
| 公開日 | 2023-12-13 |
| DOI | 10.1038/s41467-023-43630-3 |
| PII | 10.1038/s41467-023-43630-3 |
| PMID | 38092728 |
| PMC | PMC10719245 |
| MeSH | Animals Carcinoma, Neuroendocrine* / drug therapy Cell Line, Tumor Cytokines / metabolism Male Mice NAD / metabolism Niacin* / metabolism Niacin* / pharmacology Nicotinamide Phosphoribosyltransferase / metabolism |
| IF | 12.121 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Lu-134-A(RCB0466) Lu-139(RCB0469) Lu-165(RCB1184) T3M-12(RCB2281) 87-5(RCB2092) MS-1(RCB0725) S1(RCB1966) A549(RCB0098) DU145(RCB2143) LNCap.FGC(RCB2144) 293T(RCB2202) |
| 実験動物マウス | RBRC01828 |