RRC ID |
11034
|
Author |
Yoshii Y, Furukawa T, Yoshii H, Mori T, Kiyono Y, Waki A, Kobayashi M, Tsujikawa T, Kudo T, Okazawa H, Yonekura Y, Fujibayashi Y.
|
Title |
Cytosolic acetyl-CoA synthetase affected tumor cell survival under hypoxia: the possible function in tumor acetyl-CoA/acetate metabolism.
|
Journal |
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.
|
Volume |
100(5)
|
Pages |
821-7
|
Published |
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
|
Resource |
Human and Animal Cells |
B16 melanoma(RCB1283) |