| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-02-23 |
| タイトル |
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タイトル |
Metabolically inducing defects in DNA repair sensitizes -wild-type cancer cells to replication stress. |
|
言語 |
en |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 著者 |
Kenji Watanabe
Tatsuro Yamamoto
Tomoko Fujita
Shinjiro Hino
Yuko Hino
Kanami Yamazaki
Yoshimi Ohashi
Shun Sakuraba
Hidetoshi Kono
Mitsuyoshi Nakao
Koji Ochiai
Shingo Dan
Noriko Saitoh
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| 抄録 |
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内容記述タイプ |
Abstract |
|
内容記述 |
Metabolic reprogramming from oxidative respiration to glycolysis is generally considered to be advantageous for tumor initiation and progression. However, we found that breast cancer cells forced to perform glycolysis acquired a vulnerability to PARP inhibitors. Small-molecule inhibition of mitochondrial respiration-using glyceollin I, metformin, or phenformin-induced overproduction of the oncometabolite lactate, which acidified the extracellular milieu and repressed the expression of homologous recombination (HR)-associated DNA repair genes. These serial events created so-called "BRCAness," in which cells exhibit an HR deficiency phenotype despite lacking germline mutations in HR genes such as and , and, thus, sensitized the cancer cells to clinically available poly(ADP-ribose) polymerase inhibitors. The increase in lactate repressed HR-associated gene expression by decreasing histone acetylation. These effects were selective to breast cancer cells; normal epithelial cells retained HR proficiency and cell viability. These mechanistic insights into the BRCAness-prone properties of breast cancer cells support the therapeutic utility and cancer cell-specific potential of mitochondria-targeting drugs. |
| 書誌情報 |
Science signaling
巻 17,
号 862,
p. eadl6445,
発行日 2024-11
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| ISSN |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1937-9145 |
| PubMed番号 |
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識別子タイプ |
PMID |
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関連識別子 |
39531517 |
| DOI |
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|
識別子タイプ |
DOI |
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関連識別子 |
10.1126/scisignal.adl6445 |
