Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan.
Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.
Anticancer Res. 2014 Sep;34(9):4723-31.
BACKGROUND/AIM: Activation of the c-JUN N-terminal kinase (JNK) signaling pathway has been associated with poor survival of ovarian cancer patients, but the role(s) and significance of JNK signaling in ovarian cancer cells remain poorly understood. In the present study, we aimed to investigate the role of JNK specifically in ovarian cancer stem cells (CSCs).
The effect of JNK inhibition on the self-renewal (CSC marker expression, sphere-forming ability) and tumor-initiating capacity was examined in CSCs derived from the A2780 human ovarian cancer cell line. JNK inhibition was achieved either pharmacologically or genetically by use of RNA interference.
Both pharmacological and genetic targeting of JNK resulted in loss of self-renewal and tumor-initiating capacity of A2780 CSCs.
Our findings demonstrate, to our knowledge for the first time, that JNK has a pivotal role in the maintenance of ovarian CSCs.
背景/目的:c-JUN 氨基末端激酶(JNK)信号通路的激活与卵巢癌患者生存不良有关,但 JNK 信号在卵巢癌细胞中的作用和意义仍知之甚少。本研究旨在专门研究 JNK 在卵巢癌干细胞(CSC)中的作用。
使用来自人卵巢癌细胞系 A2780 的 CSC 研究了 JNK 抑制对自我更新(CSC 标志物表达、球体形成能力)和肿瘤起始能力的影响。通过使用 RNA 干扰,通过药理学或遗传学方法抑制 JNK。
JNK 的药理学和遗传靶向均导致 A2780 CSC 的自我更新和肿瘤起始能力丧失。
我们的研究结果首次表明,JNK 在维持卵巢 CSC 中起着关键作用。