Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-43630-3 |
| _version_ | 1827581505973518336 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Miyuki Nomura |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T22:37:30Z |
| format | Article |
| id | doaj.art-84428954a433469dabdd48178f38d87e |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T22:37:30Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-84428954a433469dabdd48178f38d87e2023-12-17T12:22:53ZengNature PortfolioNature Communications2041-17232023-12-0114111510.1038/s41467-023-43630-3Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinomaMiyuki Nomura0Mai Ohuchi1Yoshimi Sakamoto2Kei Kudo3Keisuke Yaku4Tomoyoshi Soga5Yuki Sugiura6Mami Morita7Kayoko Hayashi8Shuko Miyahara9Taku Sato10Yoji Yamashita11Shigemi Ito12Naohiko Kikuchi13Ikuro Sato14Rintaro Saito15Nobuo Yaegashi16Tatsuro Fukuhara17Hidekazu Yamada18Hiroshi Shima19Keiichi I. Nakayama20Atsushi Hirao21Kenta Kawasaki22Yoichi Arai23Shusuke Akamatsu24Sei-ichi Tanuma25Toshiro Sato26Takashi Nakagawa27Nobuhiro Tanuma28Division of Cancer Chemotherapy, Miyagi Cancer Center Research InstituteDivision of Cancer Chemotherapy, Miyagi Cancer Center Research InstituteDivision of Cancer Chemotherapy, Miyagi Cancer Center Research InstituteDivision of Cancer Chemotherapy, Miyagi Cancer Center Research InstituteDepartment of Molecular and Medical Pharmacology, Faculty of Medicine, University of ToyamaInstitute for Advanced Biosciences, Keio UniversityCenter for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of MedicineDivision of Cancer Chemotherapy, Miyagi Cancer Center Research InstituteDivision of Cancer Chemotherapy, Miyagi Cancer Center Research InstituteDivision of Cancer Chemotherapy, Miyagi Cancer Center Research InstituteDivision of Cancer Chemotherapy, Miyagi Cancer Center Research InstituteDivision of Cancer Chemotherapy, Miyagi Cancer Center Research InstituteDivision of Cancer Chemotherapy, Miyagi Cancer Center Research InstituteDivision of Cancer Chemotherapy, Miyagi Cancer Center Research InstituteDepartment of Pathology, Miyagi Cancer Center HospitalInstitute for Advanced Biosciences, Keio UniversityDepartment of Obstetrics and Gynecology, Tohoku University Graduate School of MedicineDepartment of Respiratory Medicine, Miyagi Cancer Center HospitalDivision of Cancer Chemotherapy, Miyagi Cancer Center Research InstituteDivision of Cancer Chemotherapy, Miyagi Cancer Center Research InstituteDepartment of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyusyu UniversityDivision of Molecular Genetics, Cancer and Stem Cell Research Program, Cancer Research Institute and WPI Nano Life Science Institute, Kanazawa UniversityDepartment of Organoid Medicine, Keio University School of MedicineDepartment of Urology, Miyagi Cancer Center HospitalDepartment of Urology, Kyoto University Graduate School of MedicineMeikai University Research Institute of OdontologyDepartment of Organoid Medicine, Keio University School of MedicineDepartment of Molecular and Medical Pharmacology, Faculty of Medicine, University of ToyamaDivision of Cancer Chemotherapy, Miyagi Cancer Center Research InstituteAbstract 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.https://doi.org/10.1038/s41467-023-43630-3 |
| spellingShingle | 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 Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma Nature Communications |
| title | Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma |
| title_full | Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma |
| title_fullStr | Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma |
| title_full_unstemmed | Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma |
| title_short | Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma |
| title_sort | niacin restriction with nampt inhibition is synthetic lethal to neuroendocrine carcinoma |
| url | https://doi.org/10.1038/s41467-023-43630-3 |
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