Casein kinase I epsilon interacts with mitochondrial proteins for the growth and survival of human ovarian cancer cells.
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.
Department of Obstetrics/Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Noah
N
Rodriguez
Junzheng
J
Yang
Kathleen
K
Hasselblatt
Shubai
S
Liu
Yilan
Y
Zhou
Jose A
JA
Rauh-Hain
Shu-Kay
SK
Ng
Pui-Wah
PW
Choi
Wing-Ping
WP
Fong
Nathalie Y R
NY
Agar
William R
WR
Welch
Ross S
RS
Berkowitz
Shu-Wing
SW
Ng
D033742:Adenine Nucleotide Translocator 2 / Q000378:metabolism*; D000818:Animals; D048149:Casein Kinase 1 epsilon / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000473:pathology; D011485:Protein Binding; D025941:Protein Interaction Mapping; D016019:Survival Analysis
D033742:Adenine Nucleotide Translocator 2; D024101:Mitochondrial Proteins; D048149:Casein Kinase 1 epsilon