Inhibition of epithelial to mesenchymal transition in metastatic prostate cancer cells by the novel proteasome inhibitor, NPI-0052: pivotal roles of Snail repression and RKIP induction

Baritaki, Stavroula; Chapman, Aaron; Yeung, Kam C.; Spandidos, Demetrios Α.; Palladino, Michael A.; Bonavida, Benjamin

doi:10.1038/onc.2009.214

Cited by 143 publications

(118 citation statements)

References 49 publications

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“…12,35,36 Treatment of prostate cancer cells with the novel proteasome inhibitor NPI-0052 was reported to induce RKIP expression via inhibition of nuclear factor-kB and Snail, leading to chemoimmunosensitation to cisplatin and TRAIL. 37 In contrast to the data on solid tumor cells, we observed growth inhibition by (re-)expression of RKIP in 32D murine hematopoietic cells and the AML cell lines U937 and THP-1, the latter characterized by RKIP loss and a mutation in NRAS. Interestingly, these effects were most pronounced under conditions of limited growth factor supply.…”

Section: Discussioncontrasting

confidence: 99%

Frequent loss of RAF kinase inhibitor protein expression in acute myeloid leukemia

et al. 2012

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RAF kinase inhibitor protein (RKIP) is a negative regulator of the RAS-mitogen-activated protein kinase/extracellular signalregulated kinase signaling cascade. We investigated its role in acute myeloid leukemia (AML), an aggressive malignancy arising from hematopoietic stem and progenitor cells (HSPCs). Western blot analysis revealed loss of RKIP expression in 19/103 (18%) primary AML samples and 4/17 (24%) AML cell lines but not in 10 CD34 þ HSPC specimens. In in-vitro experiments with myeloid cell lines, RKIP overexpression inhibited cellular proliferation and colony formation in soft agar. Analysis of two cohorts with 103 and 285 AML patients, respectively, established a correlation of decreased RKIP expression with monocytic phenotypes. RKIP loss was associated with RAS mutations and in transformation assays, RKIP decreased the oncogenic potential of mutant RAS. Loss of RKIP further related to a significantly longer relapse-free survival and overall survival in uni-and multivariate analyses. Our data show that RKIP is frequently lost in AML and correlates with monocytic phenotypes and mutations in RAS. RKIP inhibits proliferation and transformation of myeloid cells and decreases transformation induced by mutant RAS. Finally, loss of RKIP seems to be a favorable prognostic parameter in patients with AML.

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Section: Discussioncontrasting

confidence: 99%

Frequent loss of RAF kinase inhibitor protein expression in acute myeloid leukemia

et al. 2012

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“…Cell treatment with the proteasome inhibitor NPI-0052 was used as a positive control. 22 Both cell lines are characterized by constitutive activation of the NFκB signaling pathway. Treatment of DU-145 cells with DETANONOate, used at concentrations of 500 and 1,000 uM, inhibited NFκB DNA-binding activity (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Since both Snail and RKIP have been shown to regulate the EMT phenotype, [22][23][24][28][29][30][31] the DETANONOate-mediated effects on Snail and RKIP expressions and activities may lead to inhibition of EMT. To test this hypothesis, we examined the following: (1) Does DETANONOate inhibit NFκB signaling in our experimental prostate metastatic cancer cell lines used as experimental models?…”

Section: Mechanisms Of Nitric Oxide-mediated Inhibition Of Emt In Cancermentioning

confidence: 99%

Mechanisms of nitric oxide-mediated inhibition of EMT in cancer

Baritaki¹,

Huerta-Yépez²,

Sahakyan³

et al. 2010

Cell Cycle

100

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“…In non-Hodgkin's lymphoma cell lines it was shown that treatment with Rituximab induced RKIP upregulation, with further sensitization to chemotherapeutic induced apoptosis (48). Other studies reported that RKIP can be induced by nitric oxide or the proteasome inhibitor NPI-0052, via NF-κB inhibition (49)(50)(51).…”

Section: Univariate Analysis Multivariate Analysismentioning

confidence: 99%

Absence of RKIP expression is an independent prognostic biomarker for gastric cancer patients

et al. 2012

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Abstract. Gastric cancer is a leading cause of cancer-related mortality, and the presence of lymph node metastasis an important prognostic factor. Downregulation of RKIP has been associated with tumor progression and metastasis in several types of neoplasms, being currently categorized as a metastasis suppressor gene. Our aim was to determine the expression levels of RKIP in gastric tissues and to evaluate its impact in the clinical outcome of gastric carcinoma patients. RKIP expression levels were studied by immunohistochemistry in a series of gastric tissues. Overall, we analysed 222 non-neoplastic gastric tissues, 152 primary tumors and 42 lymph node metastasis samples. We observed that RKIP was highly expressed in ~83% of non-neoplastic tissues (including normal tissue and metaplasia), was lost in ~56% of primary tumors and in ~90% of lymph node metastasis samples. Loss of RKIP expression was significantly associated with several markers of poor clinical outcome, including the presence of lymph node metastasis. Furthermore, the absence of RKIP protein constitutes an independent prognostic marker for these patients. In conclusion, RKIP expression is significantly lost during gastric carcinoma progression being almost absent in lymph node metastasis samples. Of note, we showed that the absence of RKIP expression is associated with poor outcome features of gastric cancer patients, this being also an independent prognostic marker.

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Inhibition of epithelial to mesenchymal transition in metastatic prostate cancer cells by the novel proteasome inhibitor, NPI-0052: pivotal roles of Snail repression and RKIP induction

Cited by 143 publications

References 49 publications

Frequent loss of RAF kinase inhibitor protein expression in acute myeloid leukemia

Frequent loss of RAF kinase inhibitor protein expression in acute myeloid leukemia

Mechanisms of nitric oxide-mediated inhibition of EMT in cancer

Absence of RKIP expression is an independent prognostic biomarker for gastric cancer patients

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