Premium
AMP‐activated protein kinase suppresses apoptosis via feedback inhibition of c‐Jun N‐terminal kinase in glucose‐deprived cancer cells
Author(s) -
Yun Hee,
Kim SungSoo,
Ha Joohun
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a505
Subject(s) - ampk , protein kinase a , microbiology and biotechnology , apoptosis , amp activated protein kinase , kinase , c jun , cancer cell , ask1 , signal transduction , mitogen activated protein kinase kinase , chemistry , cancer research , biology , cancer , biochemistry , transcription factor , genetics , gene
As solid tumors outgrow the existing vasculature, they are continuously exposed to microenvironments where the supply of nutrients is limited, and adaptation to such environment as glucose deprivation is critical for survival of tumor cells. Nevertheless, the underlying mechanisms by which tumor cells either undergo apoptosis or survive under the glucose‐deprived condition are poorly understood. In the present study, we examined the signaling pathways leading to apoptosis after glucose deprivation in cancer cells, focusing on the role of AMP‐activated protein kinase (AMPK) and c‐Jun N‐terminal kinase (JNK). Here, we show that glucose deprivation activates JNK with biphasic kinetics; early JNK activation promotes cell survival whereas late JNK activation induces apoptosis. Inhibition of JNK at early stage under glucose‐deprived condition decreased activity of AMPK, which plays a critical role for cell survival under ATP‐depleted conditions, resulting in enhanced apoptosis in DU145 cells. Furthermore, we demonstrate that AMPK activation leads to cell survival via feedback inhibition of apoptosis‐inducing property of JNK. Taken together, our data suggest that early JNK‐mediated activation of AMPK and AMPK‐mediated inhibition of late JNK activity plays a critical role in the tumor cell survival. Thus, our results demonstrate a molecular mechanism underlying the different biological function of JNK through AMPK activation signaling.