Casein kinase I epsilon interacts with mitochondrial proteins for the growth and survival of human ovarian cancer cells
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AbstractEpithelial ovarian cancer is the leading cause of death among gynaecologic cancers in Western countries. Our studies have shown that casein kinase I-epsilon (CKIe), a Wnt pathway protein, is significantly overexpressed in ovarian cancer tissues and is associated with poor survival. Ectopic expression of CKIe in normal human ovarian surface epithelial cells and inhibition of CKIe in ovarian cancer cells and in xenografts demonstrated the importance of CKIe in regulating cell proliferation and migration. Interestingly, CKIe function did not seem to involve beta-catenin activity. Instead, CKIe was found to interact with several mitochondrial proteins including adenine nucleotide translocase 2 (ANT2). Inhibition of CKIe 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 CKIe and ANT2 mediates pathogenic signalling that is distinct from the canonical Wnt/beta-catenin pathway and is essential for cell proliferation and is clinically associated with poor survival.
All Author(s) ListRodriguez N, Yang JZ, Hasselblatt K, Liu SB, Zhou YL, Rauh-Hain JA, Ng SK, Choi PW, Fong WP, Agar NYR, Welch WR, Berkowitz RS, Ng SW
Journal nameEMBO Molecular Medicine
Volume Number4
Issue Number9
Pages952 - 963
LanguagesEnglish-United Kingdom
Keywordscasein kinase I epsilon; mitochondria; ovarian cancer; therapeutic target; Wnt signalling
Web of Science Subject CategoriesMedicine, Research & Experimental; MEDICINE, RESEARCH & EXPERIMENTAL; Research & Experimental Medicine

Last updated on 2020-28-03 at 23:12