Casein kinase I epsilon somatic mutations found in breast cancer cause overgrowth in Drosophila

Doležal, Tomáš; Kučerová, Katerina; Neuhold, Jana; Bryant, Peter J.

doi:10.1387/ijdb.093032td

Cited by 4 publications

(3 citation statements)

References 19 publications

(18 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Characterization of CKIε in breast cancer has identified several somatic mutations in the 5′‐coding region of the gene, which could lead to imaginal disc overgrowth in Drosophila (Dolezal et al, 2010; Foldynova‐Trantirkova et al, 2010; Fuja et al, 2004). We have sequenced the proposed region using DNA from 38 laser‐microdissected ovarian tumour samples and genomic DNA from 8 ovarian cancer cell lines.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2012

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

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

et al. 2012

View full text Add to dashboard Cite

show abstract

“…CSNK1e was previously implicated in WNT and SHH (for review see ref. 50) and phosphorylation of PER to regulate circadian rhythms (51,52), whereas only recently CSNK1e has been implicated in cancer (53)(54)(55). However, this is a unique demonstration of a functional link between CSNK1e and MYC to influence cancer growth and to implicate CSNK1e as a therapeutic target in MYC-driven cancers.…”

Section: Csnk1e Expression Correlates With Mycn Amplification In Neuro-mentioning

confidence: 99%

Functional genomics identifies therapeutic targets for MYC-driven cancer

Toyoshima

Howie

Imakura

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

224

205

View full text Add to dashboard Cite

MYC oncogene family members are broadly implicated in human cancers, yet are considered "undruggable" as they encode transcription factors. MYC also carries out essential functions in proliferative tissues, suggesting that its inhibition could cause severe side effects. We elected to identify synthetic lethal interactions with c-MYC overexpression (MYC-SL) in a collection of ∼3,300 druggable genes, using high-throughput siRNA screening. Of 49 genes selected for follow-up, 48 were confirmed by independent retesting and approximately one-third selectively induced accumulation of DNA damage, consistent with enrichment in DNA-repair genes by functional annotation. In addition, genes involved in histone acetylation and transcriptional elongation, such as TRRAP and BRD4, were identified, indicating that the screen revealed known MYC-associated pathways. For in vivo validation we selected CSNK1e, a kinase whose expression correlated with MYCN amplification in neuroblastoma (an established MYC-driven cancer). Using RNAi and available small-molecule inhibitors, we confirmed that inhibition of CSNK1e halted growth of MYCN-amplified neuroblastoma xenografts. CSNK1e had previously been implicated in the regulation of developmental pathways and circadian rhythms, whereas our data provide a previously unknown link with oncogenic MYC. Furthermore, expression of CSNK1e correlated with c-MYC and its transcriptional signature in other human cancers, indicating potential broad therapeutic implications of targeting CSNK1e function. In summary, through a functional genomics approach, pathways essential in the context of oncogenic MYC but not to normal cells were identified, thus revealing a rich therapeutic space linked to a previously "undruggable" oncogene.

show abstract

“…The involvement and requirement of CK1 family members in Wnt/β-catenin signaling has been studied extensively (reviewed in Clevers and Nusse, 2012 ; Knippschild et al, 2005 ; Niehrs and Acebron, 2012 ). Moreover, an increasing number of reports link altered CK1 expression or activity to cancer ( Knippschild et al, 2005 ; Dolezal et al, 2010 ; Fuja et al, 2004 ; Lin et al, 2014 ; Modak and Chai, 2009 ; Rodriguez et al, 2012 ; Schittek and Sinnberg, 2014 ), indicating that regulation and control of CK1 activity is of high importance for cells. Although CK1 isoforms were long considered to be constitutively active kinases ( Tuazon and Traugh, 1991 ), subcellular localization and post-translational modifications (especially phosphorylation) of CK1 isoforms may contribute to the regulation of their kinase activity.…”

Section: Introductionmentioning

confidence: 99%

A CK1 FRET biosensor reveals that DDX3X is an essential activator of CK1ε

Dolde

Bischof

Grüter

et al. 2018

Journal of Cell Science

View full text Add to dashboard Cite

Casein kinase 1 (CK1) plays central roles in various signal transduction pathways and performs many cellular activities. For many years CK1 was thought to act independently of modulatory subunits and in a constitutive manner. Recently, DEAD box RNA helicases, in particular DEAD box RNA helicase 3 X-linked (DDX3X), were found to stimulate CK1 activity in vitro. In order to observe CK1 activity in living cells and to study its interaction with DDX3X, we developed a CK1-specific FRET biosensor. This tool revealed that DDX3X is indeed required for full CK1 activity in living cells. Two counteracting mechanisms control the activity of these enzymes. Phosphorylation by CK1 impairs the ATPase activity of DDX3X and RNA destabilizes the DDX3X–CK1 complex. We identified possible sites of interaction between DDX3X and CK1. While mutations identified in the DDX3X genes of human medulloblastoma patients can enhance CK1 activity in living cells, the mechanism of CK1 activation by DDX3X points to a possible therapeutic approach in CK1-related diseases such as those caused by tumors driven by aberrant Wnt/β-catenin and Sonic hedgehog (SHH) activation. Indeed, CK1 peptides can reduce CK1 activity.

show abstract

Casein kinase I epsilon somatic mutations found in breast cancer cause overgrowth in Drosophila

Cited by 4 publications

References 19 publications

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

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

Functional genomics identifies therapeutic targets for MYC-driven cancer

A CK1 FRET biosensor reveals that DDX3X is an essential activator of CK1ε

Contact Info

Product

Resources

About