論文 - 詳細
| RRC ID | 11034 |
|---|---|
| 著者 | Yoshii Y, Furukawa T, Yoshii H, Mori T, Kiyono Y, Waki A, Kobayashi M, Tsujikawa T, Kudo T, Okazawa H, Yonekura Y, Fujibayashi Y. |
| タイトル | Cytosolic acetyl-CoA synthetase affected tumor cell survival under hypoxia: the possible function in tumor acetyl-CoA/acetate metabolism. |
| ジャーナル | Cancer Sci |
| Abstract |
Understanding tumor-specific metabolism under hypoxia is important to find novel targets for antitumor drug design. Here we found that tumor cells expressed higher levels of cytosolic acetyl-CoA synthetase (ACSS2) under hypoxia than normoxia. Knockdown of ACSS2 by RNA interference (RNAi) in tumor cells enhanced tumor cell death under long-term hypoxia in vitro. Our data also demonstrated that the ACSS2 suppression slowed tumor growth in vivo. These findings showed that ACSS2 plays a significant role in tumor cell survival under hypoxia and that ACSS2 would be a potential target for tumor treatment. Furthermore, we found that tumor cells excreted acetate and the quantity increased under hypoxia: the pattern of acetate excretion followed the expression pattern of ACSS2. Additionally, the ACSS2 knockdown led to a corresponding reduction in the acetate excretion in tumor cells. These results mean that ACSS2 can conduct the reverse reaction from acetyl-CoA to acetate in tumor cells, which indicates that ACSS2 is a bi-directional enzyme in tumor cells and that ACSS2 might play a buffering role in tumor acetyl-CoA/acetate metabolism. |
| 巻・号 | 100(5) |
| ページ | 821-7 |
| 公開日 | 2009-5-1 |
| DOI | 10.1111/j.1349-7006.2009.01099.x |
| PMID | 19445015 |
| MeSH | Acetate-CoA Ligase / genetics Acetate-CoA Ligase / metabolism* Acetates / metabolism* Acetyl Coenzyme A / metabolism* Animals Cell Hypoxia Cell Line, Tumor Cell Survival Cytosol / enzymology* Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Mice Neoplasms / genetics Neoplasms / metabolism* Neoplasms / pathology* RNA Interference |
| IF | 4.966 |
| リソース情報 | |
| ヒト・動物細胞 | B16 melanoma(RCB1283) |