Cytosolic acetyl-CoA synthetase affected tumor cell  survival under hypoxia: the possible function in  tumor acetyl-CoA/acetate metabolism.
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.
Yoshii
Yukie
Y
Biomedical Imaging Research Center, University of Fukui, 23-3, Shimoaizuki, Eiheiji, Fukui 910-1193, Japan.
Furukawa
Takako
T
Yoshii
Hiroshi
H
Mori
Tetsuya
T
Kiyono
Yasushi
Y
Waki
Atsuo
A
Kobayashi
Masato
M
Tsujikawa
Tetsuya
T
Kudo
Takashi
T
Okazawa
Hidehiko
H
Yonekura
Yoshiharu
Y
Fujibayashi
Yasuhisa
Y
D000106:Acetate-CoA Ligase / Q000235:genetics / Q000378:metabolism*; D000085:Acetates / Q000378:metabolism*; D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival; D003600:Cytosol / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D034622:RNA Interference
D000085:Acetates; D000105:Acetyl Coenzyme A; D000106:Acetate-CoA Ligase