Association of Nuclear-Localized Nemo-Like Kinase with Heat-Shock Protein 27 Inhibits Apoptosis in Human Breast Cancer Cells

Shaw-Hallgren, Gina; Masoumi, Katarzyna Chmielarska; Zarrizi, Reihaneh; Hellman, Ulf; Karlsson, Per; Helou, Khalil; Massoumi, Ramin

doi:10.1371/journal.pone.0096506

Cited by 19 publications

(10 citation statements)

References 40 publications

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“…Nemo is a serine/threonine kinase essential for programmed cell death and eye development in Drosophila [ 19 , 20 ]. NLK is the mammalian orthologue of Drosophila nemo implicated in multiple physiological processes [ 21 – 23 ]. We suspected that NLK might play a regulatory role in the heart given an observed upregulation of its expression following 2 weeks of pressure overload hypertrophy induced by transverse aortic constriction (TAC) and 1 week after myocardial infarction (MI) injury ( Fig 1A and 1B ).…”

Section: Resultsmentioning

confidence: 99%

Nemo-Like Kinase (NLK) Is a Pathological Signaling Effector in the Mouse Heart

et al. 2016

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Nemo-like kinase (NLK) is an evolutionary conserved serine/threonine protein kinase implicated in development, proliferation and apoptosis regulation. Here we identified NLK as a gene product induced in the hearts of mice subjected to pressure overload or myocardial infarction injury, suggesting a potential regulatory role with pathological stimulation to this organ. To examine the potential functional consequences of increased NLK levels, cardiac-specific transgenic mice with inducible expression of this gene product were generated, as well as cardiac-specific Nlk gene-deleted mice. NLK transgenic mice demonstrated baseline cardiac hypertrophy, dilation, interstitial fibrosis, apoptosis and progression towards heart failure in response to two surgery-induced cardiac disease models. In contrast, cardiac-specific deletion of Nlk from the heart, achieved by crossing a Nlk-loxP allele containing mouse with either a mouse containing a β-myosin heavy chain promoter driven Cre transgene or a tamoxifen inducible α-myosin heavy chain promoter containing transgene driving a MerCreMer cDNA, protected the mice from cardiac dysfunction following pathological stimuli. Mechanistically, NLK interacted with multiple proteins including the transcription factor Stat1, which was significantly increased in the hearts of NLK transgenic mice. These results indicate that NLK is a pathological effector in the heart.

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Section: Resultsmentioning

confidence: 99%

Nemo-Like Kinase (NLK) Is a Pathological Signaling Effector in the Mouse Heart

et al. 2016

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“…HSPB1 is a promising diagnostic marker for clear cell renal cell carcinoma, although further large-scale studies are required (White et al, 2014). A novel mechanism by which HSPB1 recognizes Nemolike kinase in breast cancer cells and prevents Nemo-like kinase-mediated cell apoptosis has been described (Shaw-Hallgren et al, 2014). A large number of researchers have paid close attention to HSPB1 inhibitor in the context of renal carcinoma, breast cancer, cervical cancer, etc.…”

Section: Discussionmentioning

confidence: 99%

Potential role of heat-shock proteins in giant cell tumors

et al. 2015

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ABSTRACT. We investigated the differential expression protein profile of giant cell tumors (GCTs), which can be used to monitor the tumor's recurrence and metastasis, to provide preliminary results for further study. We also explored heat-shock protein (HSP) inhibitor that prevents tumors from recurring and migrating. A stable isotope-labeling strategy using isobaric tags for relative and absolute quantitation coupled with twodimensional liquid chromatography tandem mass spectrometry was used to separate and identify differentially expressed proteins. A total of 467 differentially expressed proteins were identified in GCT tissues. Up to 311 proteins were upregulated, whereas 156 proteins were downregulated in GCT tissues. Three of the differentially expressed HSPs, namely HP90A, HSPB1, and HSPB2, were upregulated. The differentially expressed proteins of GCT tissues will provide a scientific foundation for tumor prognosis, and for further studies exploring HSP inhibitor to prevent tumor recurrence and migration.

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“…Hsp27 can recognize and bind to NLK and then suppress NLK translocation from the nucleus to the cytosol. Downregulation of HSP27 released NLK to the cytosol, which triggered apoptosis and death in MCF-7 cells [15] (Fig. 1).…”

Section: Upstream Regulators Of Nlk In Cancersmentioning

confidence: 98%

“…In ovarian cancer, NLK is predominant in the nucleus that is downregulated compared to normal human ovarian tissues, and patients with low NLK expression have poorer outcome than those with NLK overexpression [13]. NLK is mainly expressed in the nuclei and is significantly downregulated in the breast cancer tissues compared to corresponding normal tissues [14,15]. The staining intensity of NLK is higher in breast benign tumor tissues than in carcinoma specimens, which may contribute to the progression of breast carcinoma [14].…”

Section: Altered Expression Of Nlk In Cancersmentioning

confidence: 99%

The emerging role of Nemo-like kinase (NLK) in the regulation of cancers

Huang

Yang

et al. 2015

Tumor Biol.

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Nemo-like kinase (NLK) is an evolutionarily conserved mitogen-activated protein (MAP) kinase-related kinase that is highly expressed in neural tissues and minimally detected in others. Accumulating evidence demonstrates that NLK exerts a pivotal role in cell proliferation, migration, invasion, and apoptosis via regulation of a variety of transcriptional molecules. The results of recent studies have shown that aberrant expression of NLK is significantly associated with the initiation and progression of various types of human cancers, as well as clinicopathologic features and survival rate. NLK is gradually considered as a potential tumor suppressor or an oncogene depending on the tumor system, and silencing or upregulating of NLK may provide an effective therapeutic approach against tumors. In this review, we will make a summary on the comprehensive roles of NLK in the regulation of various cancers.

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Association of Nuclear-Localized Nemo-Like Kinase with Heat-Shock Protein 27 Inhibits Apoptosis in Human Breast Cancer Cells

Cited by 19 publications

References 40 publications

Nemo-Like Kinase (NLK) Is a Pathological Signaling Effector in the Mouse Heart

Nemo-Like Kinase (NLK) Is a Pathological Signaling Effector in the Mouse Heart

Potential role of heat-shock proteins in giant cell tumors

The emerging role of Nemo-like kinase (NLK) in the regulation of cancers

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