Manabu Seino1, Masashi Okada2, Keita Shibuya3, Shizuka Seino4, Shuhei Suzuki5, Tsuyoshi Ohta6, Hirohisa Kurachi7, Chifumi Kitanaka8. 1. Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan. 2. Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan. 3. Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Oncology Research Center, Research Institute for Advanced Molecular Epidemiology, Yamagata University, Yamagata, Japan Global COE program for Medical Sciences, Japan Society for Promotion of Science, Tokyo, Japan. 4. Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Oncology Research Center, Research Institute for Advanced Molecular Epidemiology, Yamagata University, Yamagata, Japan Global COE program for Medical Sciences, Japan Society for Promotion of Science, Tokyo, Japan Research Institute for Promotion of Medical Sciences, Yamagata University School of Medicine, Yamagata, Japan. 5. Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan Department of Regional Cancer Network, Yamagata University School of Medicine, Yamagata, Japan. 6. Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan. 7. Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan. 8. Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan Oncology Research Center, Research Institute for Advanced Molecular Epidemiology, Yamagata University, Yamagata, Japan Global COE program for Medical Sciences, Japan Society for Promotion of Science, Tokyo, Japan Research Institute for Promotion of Medical Sciences, Yamagata University School of Medicine, Yamagata, Japan ckitanak@med.id.yamagata-u.ac.jp.
Abstract
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). MATERIALS AND METHODS: 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. RESULTS: Both pharmacological and genetic targeting of JNK resulted in loss of self-renewal and tumor-initiating capacity of A2780 CSCs. CONCLUSION: Our findings demonstrate, to our knowledge for the first time, that JNK has a pivotal role in the maintenance of ovarian CSCs. Copyright
BACKGROUND/AIM: Activation of the c-JUN N-terminal kinase (JNK) signaling pathway has been associated with poor survival of ovarian cancerpatients, 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). MATERIALS AND METHODS: 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 humanovarian cancer cell line. JNK inhibition was achieved either pharmacologically or genetically by use of RNA interference. RESULTS: Both pharmacological and genetic targeting of JNK resulted in loss of self-renewal and tumor-initiating capacity of A2780 CSCs. CONCLUSION: Our findings demonstrate, to our knowledge for the first time, that JNK has a pivotal role in the maintenance of ovarian CSCs. Copyright