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

Rodriguez, Noah; Yang, Junzheng; Hasselblatt, Kathleen T; Liu, Shubai; Zhou, Yi; Rauh-Hain, Jose Alejandro; Ng, Shu Kay; Choi, Pui Wah; Fong, Wing‐Ping; Agar, Nathalie Y.R.; Welch, William R.; Berkowitz, Ross S.; Ng, Sook Kien

doi:10.1002/emmm.201101094

Cited by 54 publications

(53 citation statements)

References 47 publications

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“…Our results are consistent with the data of Lin and coworkers, who recently demonstrated that CK1ɛ expression in oral cancer is related to considerably better overall survival compared to patients with CK1ɛ negative tumors . Contrarily, Rodriguez and coworkers showed that overexpression of CK1ɛ in ovarian cancer is associated with poor survival, strengthening the hypothesis that the role of CK1ɛ in carcinogenesis varies in different cancer entities.…”

Section: Discussionsupporting

confidence: 92%

Effects of altered expression and activity levels of CK1δ and ɛ on tumor growth and survival of colorectal cancer patients

Richter

Ullah

et al. 2014

Intl Journal of Cancer

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Colorectal cancer (CRC) is the fourth leading cause of cancer related death worldwide due to high apoptotic resistance and metastatic potential. Because mutations as well as deregulation of CK1 isoforms contribute to tumor development and tumor progression, CK1 has become an interesting drug target. In this study we show that CK1 isoforms are differently expressed in colon tumor cell lines and that growth of these cell lines can be inhibited by CK1-specific inhibitors. Furthermore, expression of CK1d and E is changed in colorectal tumors compared to normal bowel epithelium, and high CK1E expression levels significantly correlate with prolonged patients' survival. In addition to changes in CK1d and E expression, mutations within exon 3 of CK1d were detected in colorectal tumors. These mutations influence ATP binding resulting in changes in kinetic parameters of CK1d. Overexpression of these mutants in HT29 cells alters their ability to grow anchorage independently. Consistent with these results, these CK1d mutants lead to differences in proliferation rate and tumor size in xenografts due to changes in gene expression, especially in genes involved in regulation of cell proliferation, cell cycle, and apoptosis. In summary, our results provide evidence that changes in the expression levels of CK1 isoforms in colorectal tumors correlate with patients' survival. Furthermore, CK1 mutants affect growth and proliferation of tumor cells and induce tumor growth in xenografts, leading to the assumption that CK1 isoforms provide interesting targets for the development of novel effective therapeutic concepts to treat colorectal cancer.Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer related death in both men and women worldwide. 1,2 Since the 5-year survival rate of metastatic CRC is only about 10%, it is important to receive detailed information on molecular level regarding its carcinogenesis and progression and to search for new effective therapy concepts. Although modern treatment schemes have resulted in prolonged median survival of patients, the overall prognosis is still poor. Because of high apoptotic resistance and metastatic potential conventional chemotherapeutic concepts are often ineffective in the treatment of CRC, or are associated with severe side effects. Therefore, research efforts are currently focusing on the identification of novel target molecules. In line with this notion, drug discovery projects aiming to develop effective and isoform-specific CK1 inhibitors have drawn considerable interest. Members of the serine/threonine-specific CK1 family are evolutionary highly conserved and ubiquitously expressed in eukaryotic organisms. So far, seven distinct genes encoding mammalian CK1 isoforms a, b, g1, g2, g3, d, E and various splice variants have been characterized. CK1 isoforms play major regulatory

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Section: Discussionsupporting

confidence: 92%

Effects of altered expression and activity levels of CK1δ and ɛ on tumor growth and survival of colorectal cancer patients

Richter

Ullah

et al. 2014

Intl Journal of Cancer

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“…In some types of cancer, CK1α seems to exhibit oncogenic features by promoting proliferation, genome instability and inhibition of apoptotic processes, such as ovarian cancer, 26 acute myelocytic leukemia 27 and so on, which are supported by the fact that CK1α is often overexpressed in those tumors and correlates with poor survival. Although in some other types of cancer, such as colorectal carcinoma, lymphomas and breast carcinomas, 28 CK1α acts as a tumor suppressor which is evidenced by the fact that loss of heterozygosity of CK1α gene causes a highly invasive carcinoma and reduced CK1α expression was often observed in those tumors.…”

Section: Discussionmentioning

confidence: 99%

The interplay between HPIP and casein kinase 1α promotes renal cell carcinoma growth and metastasis via activation of mTOR pathway

Mai

Xu²,

Guo-Hui

et al. 2016

Oncogenesis

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Hematopoietic pre-B cell leukemia transcription factor (PBX)-interacting protein (HPIP) was shown to be crucial during the development and progression of a variety of tumors. However, the role of HPIP in renal cell carcinoma (RCC) is unknown. Here we report that HPIP is upregulated in most RCC patients, positively correlates with tumor size, high Fuhrman grade and preoperative metastasis, and predicts poor clinical outcomes. Mechanistically, we identified casein kinase 1α (CK1α), a critical regulator of tumorigenesis and metastasis, as a novel HPIP-interacting protein. HPIP facilitates RCC cell growth, migration, invasion and epithelial–mesenchymal transition depending on its interaction with CK1α. Activation of mammalian target of rapamycin pathways by HPIP is partly dependent on CK1α and is required for HPIP modulation of RCC cell proliferation and migration. HPIP knockdown suppresses renal tumor growth and metastasis in nude mice through CK1α. Moreover, expression of CK1α is positively correlated with HPIP in RCC samples, and also predicts poor clinical outcome-like expression of HPIP. Taken together, our data demonstrate the critical regulatory role of the HPIP–CK1α interaction in RCC, and suggest that HPIP and CK1α may be potential targets for RCC therapy.

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“…For example, while previous literature identifies CSNK1e as a modulator of circadian rhythms (Preuss et al 2004) (Badura et al 2007) (Meng et al 2008), more recent studies do not confirm its essential role in this pathway (Sekine et al 2008) (Walton et al 2009). In contrast, CSNK1e has been implicated in cancer, both in ovarian (Rodriguez et al 2012) and in breast cancer, where its function is linked to the activity of the WNT pathway (Kim et al). CSNK1e has also been shown to be required for transcriptional response to hedgehog (HH) signaling (Varjosalo et al 2008) and in this respect, it is worthwhile to point out that GLI1, the main transcriptional mediator of HH signaling, also emerged as MYC-SL gene.…”

Section: Myc Synthetic Lethal Genes and The Hallmarks Of Mycmentioning

confidence: 99%

Synthetic Lethal Screens as a Means to Understand and Treat MYC-Driven Cancers

Cermelli

Jang

Bernard

et al. 2014

Cold Spring Harbor Perspectives in Medicine

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While therapeutics against MYC could potentially be employed against a wide range of human cancers, MYC targeted therapies have proven difficult to develop. The convergence of breakthroughs in human genomics and in gene silencing using RNA interference (RNAi), have recently allowed functional interrogation of the genome and systematic identification of synthetic lethal interactions with hyper-active MYC. Here, we focus on the pathways that have emerged through RNAi screens and present evidence that a subset of genes exhibiting synthetic lethality with MYC are significantly interconnected and linked to chromatin, and transcriptional processes, as well as to DNA repair and cell-cycle checkpoints. Other synthetic lethal interactions with MYC point to novel pathways and potentially broaden the repertoire of targeted therapies. The elucidation of MYC synthetic lethal interactions is still in its infancy and how these interactions may be influenced by tissue specific programs and by concurrent genetic change will require further investigation. Nevertheless, we predict that these studies may lead the way to novel therapeutic approaches and new insights into the role of MYC in cancer.

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

Cited by 54 publications

References 47 publications

Effects of altered expression and activity levels of CK1δ and ɛ on tumor growth and survival of colorectal cancer patients

Effects of altered expression and activity levels of CK1δ and ɛ on tumor growth and survival of colorectal cancer patients

The interplay between HPIP and casein kinase 1α promotes renal cell carcinoma growth and metastasis via activation of mTOR pathway

Synthetic Lethal Screens as a Means to Understand and Treat MYC-Driven Cancers

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