Journal
CANCER SCIENCE
Volume 100, Issue 5, Pages 821-827Publisher
WILEY
DOI: 10.1111/j.1349-7006.2009.01099.x
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Funding
- Japan Society for the Promotion of Science (JSPS), Japan
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Japan Science and Technology Agency, Japan
- Ministry of Health, Labour and Welfare, Japan
- Grants-in-Aid for Scientific Research [21390342] Funding Source: KAKEN
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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. (Cancer Sci 2009; 100: 821-827).
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