RKIP does not contribute to MAP kinase pathway silencing in the Merkel Cell Carcinoma cell line UISO

Houben, Roland; Ortmann, Sonja; Becker, Juergen C.

doi:10.1186/1477-3163-6-16

Cited by 9 publications

(7 citation statements)

References 15 publications

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“…The lack of ERK phosphorylation was always accompanied by a strong expression of the Raf kinase inhibitor protein (RKIP), a negative regulator of the MAPK cascade. However, silencing of RKIP did not lead to an induction of ERK phosphorylation [31]. The general inactivity of the "mitogenic" cascade distinguishes MCC from many other tumors such as melanoma and raises the question if active MAP kinase signaling is perhaps even a negative selection factor for MCC cells.…”

Section: Pathogenesismentioning

confidence: 98%

Merkel cell carcinoma

Becker

Schrama

Houben

2008

Cell. Mol. Life Sci.

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Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin. More than one-third of MCC patients will die from this cancer, making it twice as lethal as malignant melanoma. Despite the fact that MCC is still a very rare tumor, its incidence is rapidly increasing; the American Cancer Society estimates for 2008 almost 1,500 new cases in the USA. These clinical observations are especially disturbing as the pathogenesis of MCC is not yet fully understood; however, a number of recent reports contribute to a better understanding of its pathogenesis. Here we describe findings regarding the role of Wnt, MAPK and Akt signaling as well as possible aberrations in the p14ARF/p53/RB tumor suppressor network in MCC. Most important, and possibly with high impact on future therapeutic approaches is the demonstration that a polyomavirus has frequently integrated in the genome of the MCC cells prior to tumor development.

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Section: Pathogenesismentioning

confidence: 98%

Merkel cell carcinoma

Becker

Schrama

Houben

2008

Cell. Mol. Life Sci.

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“…In addition, RKIP overexpression in C4-2B cells led to reduced cell invasion in vitro. Interestingly, a Merkel carcinoma line was identified that overexpressed RKIP and lost ERK signaling; however, further studies revealed that RKIP depletion did not rescue the ERK signaling defect consistent with RKIP's role as a modulator rather than suppressor of the MAPK pathway [34]. Finally, a recent study showed that Snail, a mediator of the epithelial-mesenchymal transition (EMT), can inhibit RKIP transcription and negatively correlates with RKIP levels in tumors, consistent with a role for RKIP in metastasis [35].…”

mentioning

confidence: 99%

Raf kinase inhibitory protein: a signal transduction modulator and metastasis suppressor

2008

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Cells have a multitude of controls to maintain their integrity and prevent random switching from one biological state to another. Raf Kinase Inhibitory Protein (RKIP), a member of the phosphatidylethanolamine binding protein (PEBP) family, is representative of a new class of modulators of signaling cascades that function to maintain the "yin yang" or balance of biological systems. RKIP inhibits MAP kinase (Raf-MEK-ERK), G protein-coupled receptor (GPCR) kinase and NFκB signaling cascades. Because RKIP targets different kinases dependent upon its state of phosphorylation, RKIP also acts to integrate crosstalk initiated by multiple environmental stimuli. Loss or depletion of RKIP results in disruption of the normal cellular stasis and can lead to chromosomal abnormalities and disease states such as cancer. Since RKIP and the PEBP family have been reviewed previously, the goal of this analysis is to provide an update and highlight some of the unique features of RKIP that make it a critical player in the regulation of cellular signaling processes.

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“…Furthermore, the expression levels of NF-κB were negatively correlated with those of RKIP. Several mechanisms might be invoked to explain how RKIP could regulate the occurrence and development of DN, including RKIP coupling with NF-κB-inducing kinase, TGF-D-activated kinase 1, I-κB kinase, and I-κB kinase β, which are all involved in inhibition of NF-κB signal transduction (Yeung et al, 2001;Corbit et al, 2003;Lorenz et al, 2003;Houben et al, 2007;Matallanas et al, 2011;Fujimori et al, 2012). Downregulation of RKIP might trigger the NF-κB pathway in DN, which then activates the I-κB kinase.…”

Section: Discussionmentioning

confidence: 99%

Rituximab regulates the expression of the Raf kinase inhibitor protein via NF-κB in renal tissue of rats with diabetic nephropathy

Li¹,

Zhao²,

Zeng³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. This study aimed to investigate the expression levels of the Raf kinase inhibitor protein (RKIP) and NF-κB in renal tissues of diabetic nephropathy (DN) rats, and to determine the underlying molecular targets of rituximab (RTX), with the goal of developing new clinical treatment selection for DN. SpragueDawley rats were randomly divided into a normal group (N), a DN group (M), and an RTX treatment group (D). Blood glucose and 24-h urine protein levels of rats were determined. The expression levels of RKIP and NF-κB in glomerular tissues were determined by immunohistochemistry staining and Western blotting. Comparisons between the M and N groups revealed that the concentrations of blood glucose and 24-h urine protein were significantly increased by DN (P < 0.01), and the expression levels of RKIP and NF-κB were significantly decreased and increased (P < 0.05), respectively. In the D group, the expression levels of RKIP and NF-κB were, respectively, upregulated and downregulated by RTX, and the concentrations of 24-h urine protein were also decreased by RTX. These results suggest that expression levels of RKIP might be regulated by RTX via NF-κB. This pathway could play an important role in the development and pathogenesis of DN. Therefore, RTX could be selected for clinical treatment of DN.

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RKIP does not contribute to MAP kinase pathway silencing in the Merkel Cell Carcinoma cell line UISO

Cited by 9 publications

References 15 publications

Merkel cell carcinoma

Merkel cell carcinoma

Raf kinase inhibitory protein: a signal transduction modulator and metastasis suppressor

Rituximab regulates the expression of the Raf kinase inhibitor protein via NF-κB in renal tissue of rats with diabetic nephropathy

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