Requirement of JNK signaling for self-renewal and tumor-initiating capacity of ovarian cancer stem cells.

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.

• Authors: Manabu Seino, Masashi Okada, Keita Shibuya, Shizuka Seino, Shuhei Suzuki, Tsuyoshi Ohta, Hirohisa Kurachi, Chifumi Kitanaka
• Journal: Anticancer research (Anticancer Res) Vol. 34 Issue 9 Pg. 4723-31 (Sep 2014) ISSN: 1791-7530 [Electronic] Greece
• PMID: 25202050 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• Anthracenes
• pyrazolanthrone
• JNK Mitogen-Activated Protein Kinases

Topics

• Animals
• Anthracenes (pharmacology)
• Cell Line, Tumor
• Cell Transformation, Neoplastic (genetics, metabolism)
• Disease Models, Animal
• Enzyme Activation (drug effects)
• Female
• Gene Knockdown Techniques
• Heterografts
• Humans
• JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors, genetics, metabolism)
• Mice
• Neoplastic Stem Cells (drug effects, metabolism)
• Ovarian Neoplasms (genetics, metabolism, mortality, pathology)
• Signal Transduction
• Spheroids, Cellular
• Tumor Burden (drug effects, genetics)
• Tumor Cells, Cultured