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

• DOI: 10.1002/emmm.201101094
• Publication Date: 2012-06-18T08:45:59Z
• Authors: Noah Rodriguez; Junzheng Yang; Kathleen Hasselblatt; Shubai Liu; Yilan Zhou; Jose A. Rauh‐Hain; Shu‐Kay Ng; Pui‐Wah Choi; Wing‐Ping Fong; Nathalie Y. R. Agar; William R. Welch; Ross S. Berkowitz; Shu‐Wing Ng
• Keywords: 0301 basic medicine; Medicine (General); Biomedical and clinical sciences; Casein Kinase 1 epsilon; Cell Survival; casein kinase I epsilon; Mice, Nude; QH426-470; Mitochondrial Proteins; Mice; 03 medical and health sciences; R5-920; Cell Line, Tumor; Protein Interaction Mapping; Genetics; Animals; Humans; Wnt signalling; Research Articles; Cell Proliferation; Ovarian Neoplasms; therapeutic target; Adenine Nucleotide Translocator 2; Epithelial Cells; Survival Analysis; 3. Good health; mitochondria; Biological sciences; ovarian cancer; Female; Protein Binding

AbstractEpithelial 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.