Cytosolic acetyl-CoA synthetase affected tumor cell survival under hypoxia: the possible function in tumor acetyl-CoA/acetate metabolism.
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| 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.
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| Authors | Yukie Yoshii, Takako Furukawa, Hiroshi Yoshii, Tetsuya Mori, Yasushi Kiyono, Atsuo Waki, Masato Kobayashi, Tetsuya Tsujikawa, Takashi Kudo, Hidehiko Okazawa, Yoshiharu Yonekura, Yasuhisa Fujibayashi |
| Journal | Cancer science (Cancer Sci) Vol. 100 Issue 5 Pg. 821-7 (May 2009) ISSN: 1349-7006 [Electronic] England |
| PMID | 19445015 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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