Casein kinase I epsilon interacts with mitochondrial proteins for the growth and survival of human ovarian cancer cells

EMBO Molecular Medicine

Noah Rodriguez²  Junzheng Yang²  Kathleen Hasselblatt²  Shubai Liu²  Yilan Zhou²  Jose A. Rauh-Hain²  Shu-Kay Ng³  Pui-Wah Choi⁴  Wing-Ping Fong⁴  Nathalie Y. R. Agar¹  William R. Welch⁵  Ross S. Berkowitz² 

[1] Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA;Department of Obstetrics/Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts, USA;School of Medicine, Griffith Health Institute, Griffith University, Meadowbrook, Australia;School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China;Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA

关键词: casein kinase I epsilon;    mitochondria;    ovarian cancer;    therapeutic target;    Wnt signalling;   

DOI  :  10.1002/emmm.201101094

来源: Wiley

【 摘 要 】

Abstract

Epithelial ovarian cancer is the leading cause of death among gynaecologic cancers in Western countries. Our studies have shown that casein kinase I-epsilon (CKIε), a Wnt pathway protein, is significantly overexpressed in ovarian cancer tissues and is associated with poor survival. Ectopic expression of CKIε in normal human ovarian surface epithelial cells and inhibition of CKIε in ovarian cancer cells and in xenografts demonstrated the importance of CKIε in regulating cell proliferation and migration. Interestingly, CKIε function did not seem to involve β-catenin activity. Instead, CKIε was found to interact with several mitochondrial proteins including adenine nucleotide translocase 2 (ANT2). Inhibition of CKIε in ovarian cancer cells resulted in suppression of ANT2, downregulation of cellular ATP and the resulting cancer cells were more susceptible to chemotherapy. Our studies indicate that, in the context of ovarian cancer, the interaction between CKIε and ANT2 mediates pathogenic signalling that is distinct from the canonical Wnt/β-catenin pathway and is essential for cell proliferation and is clinically associated with poor survival.

【 授权许可】

CC BY   
Copyright © 2012 EMBO Molecular Medicine

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