Open AccessCytosolic acetyl‐CoA synthetase affected tumor cell survival under hypoxia: the possible function in tumor acetyl‐CoA/acetate metabolism
Author(s) -
Yoshii Yukie,
Furukawa Takako,
Yoshii Hiroshi,
Mori Tetsuya,
Kiyono Yasushi,
Waki Atsuo,
Kobayashi Masato,
Tsujikawa Tetsuya,
Kudo Takashi,
Okazawa Hidehiko,
Yonekura Yoshiharu,
Fujibayashi Yasuhisa
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01099.x
Subject(s) - gene knockdown , rna interference , hypoxia (environmental) , biology , cell , cell culture , in vivo , metabolism , cancer research , cell growth , in vitro , microbiology and biotechnology , biochemistry , chemistry , apoptosis , rna , gene , oxygen , genetics , organic chemistry
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)