| Autor: |
Miyuki Nomura, Mai Ohuchi, Yoshimi Sakamoto, Kei Kudo, Keisuke Yaku, Tomoyoshi Soga, Yuki Sugiura, Mami Morita, Kayoko Hayashi, Shuko Miyahara, Taku Sato, Yoji Yamashita, Shigemi Ito, Naohiko Kikuchi, Ikuro Sato, Rintaro Saito, Nobuo Yaegashi, Tatsuro Fukuhara, Hidekazu Yamada, Hiroshi Shima, Keiichi I. Nakayama, Atsushi Hirao, Kenta Kawasaki, Yoichi Arai, Shusuke Akamatsu, Sei-ichi Tanuma, Toshiro Sato, Takashi Nakagawa, Nobuhiro Tanuma |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-15 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-023-43630-3 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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