Nm23-M2/NDP kinase B induces endogenous c-myc and nm23-M1/NDP kinase A overexpression in BAF3 cells. Both NDP kinases protect the cells from oxidative stress-induced death

Arnaud-Dabernat, Sandrine; Massé, Karine; Smani, Moneïm; Peuchant, Evelyne; Landry, Marc; Bourbon, P; Floch, Renaud Le; Daniel, Jean-Yves; Larou, Monique

doi:10.1016/j.yexcr.2004.07.026

Cited by 33 publications

(30 citation statements)

References 34 publications

(44 reference statements)

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“…We chose to focus on Nm23 for several reasons, the first of which being that, in a variety of different cancers, a decrease in both Nm23 and cadherin-mediated adhesion is observed, whereas the genes encoding these proteins remain unaltered (Chen et al, 2005;Che et al, 2006). Previous studies have also shown that Nm23 is both targeted by and regulates c-myc, which was the first identified target of the Wnt/b-catenin signaling network (He et al, 1998;Schuldiner et al, 2002;Arnaud-Dabernat et al, 2004). In addition, we recently showed that the levels and subcellular localization of Figure 5 a-Catenin is necessary for the interaction between plakoglobin and Nm23.…”

Section: Discussionmentioning

confidence: 85%

Plakoglobin interacts with and increases the protein levels of metastasis suppressor Nm23-H2 and regulates the expression of Nm23-H1

et al. 2010

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Plakoglobin (c-catenin) is a homolog of b-catenin with similar dual adhesive and signaling functions. The adhesive function of these proteins is mediated by their interactions with cadherins, whereas their signaling activity is regulated by association with various intracellular partners. In this respect, b-catenin has a well-defined oncogenic activity through its role in the Wnt signaling pathway, whereas plakoglobin acts as a tumor/metastasis suppressor through mechanisms that remain unclear. We previously expressed plakoglobin in SCC9 squamous carcinoma cells (SCC9-P) and observed a mesenchymalto-epidermoid transition. Comparison of the protein and RNA profiles of parental SCC9 cells and SCC9-P transfectants identified various differentially expressed proteins and transcripts, including the nonmetastatic protein 23 (Nm23). In this study, we show that Nm23-H1 mRNA and Nm23-H2 protein are increased after plakoglobin expression. Coimmunoprecipitation and confocal microscopy studies using SCC9-P and various epithelial cell lines with endogenous plakoglobin expression revealed that Nm23 interacts with plakoglobin, cadherins and a-catenin. Furthermore, Nm23-H2 is the primary isoform involved in these interactions, which occur prominently in the cytoskeleton-associated pool of cellular proteins. In addition, we show that plakoglobinNm23 interaction requires the N-terminal (a-catenin interacting) domain of plakoglobin. Our data suggest that by increasing the expression and stability of Nm23, plakoglobin has a role in regulating the metastasis suppressor activity of Nm23, which may further provide a potential mechanism for the tumor/metastasis suppressor function of plakoglobin itself.

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Section: Discussionmentioning

confidence: 85%

Plakoglobin interacts with and increases the protein levels of metastasis suppressor Nm23-H2 and regulates the expression of Nm23-H1

et al. 2010

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“…In addition, previous reports indicated that some other proteins identified by the present proteome analysis (Table 2) could be activated by oxidative stress. [30][31][32][33][34] For example, NDPKA is reported to be activated by ROS and protected the cell from ROS-induced apoptosis. 30,31 CLIC1 protein contains a redox-active site and is activated during ROS-triggered apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…[30][31][32][33][34] For example, NDPKA is reported to be activated by ROS and protected the cell from ROS-induced apoptosis. 30,31 CLIC1 protein contains a redox-active site and is activated during ROS-triggered apoptosis. 32,33 These findings suggested a possibility that NCH-51 might induce the cytotoxic effect by modulating the intracellular ROS content.…”

Section: Discussionmentioning

confidence: 99%

Proteome analyses of the growth inhibitory effects of NCH-51, a novel histone deacetylase inhibitor, on lymphoid malignant cells

et al. 2007

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Recent reports showing successful inhibition of cancer and leukemia cell growth using histone deacetylase inhibitor (HDACi) compounds have highlighted the potential use of HDACi as anti-cancer agents. However, high incidence of toxicity and low stability in vivo were observed with hydroxamic acid-based HDACi such as suberoylanilide hydroxamic acid (SAHA), thus limiting its clinical applicability. In this study, we found that a novel non-hydroxamate HDACi NCH-51 could inhibit the cell growth of a variety of lymphoid malignant cells through apoptosis induction, more effectively than SAHA. Activation of caspase-3, -8 and -9, but not -7 was detected after the treatment with NCH-51. Gene expression profiles showed that NCH-51 and SAHA similarly upregulated p21 and downregulated anti-apoptotic molecules including survivin, bcl-w and c-FLIP. Proteome analysis using two-dimensional electrophoresis revealed that NCH-51 upregulated anti-oxidant molecules including peroxiredoxin 1 and 2 and glutathione S-transferase at the protein level. Interestingly, NCH-51 induced reactive oxygen species (ROS) after 8 h whereas SAHA continuously declined ROS. Pretreatment with an antioxidant, N-acetyl-L-cysteine, abolished the cytotoxicity of NCH-51. These findings suggest that NCH-51 exhibits cytotoxicity by sustaining ROS at the higher level greater than SAHA. This study indicates the therapeutic efficacy of NCH-51 and novel insights for anti-HDAC therapy.

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“…The different responses to stauprimide in different cells may be attributable to the diversity of signaling cascades, transcriptional programs, and epigenetic modifications regulating MYC promotor activities in different cellular contexts (32). Furthermore, stauprimide suppresses MYC transcription in murine cancer cells, including the melanoma cell line B16 and lung cancer cell line MLE12 at concentrations and magnitudes comparable to those in their human counterparts, suggesting relatively conserved MYC transcription regulation across species (33,34).…”

mentioning

confidence: 99%

Small molecule selectively suppresses MYC transcription in cancer cells

Bouvard

Lim

Ludka

et al. 2017

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

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Stauprimide is a staurosporine analog that promotes embryonic stem cell (ESC) differentiation by inhibiting nuclear localization of the MYC transcription factor NME2, which in turn results in downregulation of MYC transcription. Given the critical role the oncogene MYC plays in tumor initiation and maintenance, we explored the potential of stauprimide as an anticancer agent. Here we report that stauprimide suppresses MYC transcription in cancer cell lines derived from distinct tissues. Using renal cancer cells, we confirmed that stauprimide inhibits NME2 nuclear localization. Gene expression analysis also confirmed the selective down-regulation of MYC target genes by stauprimide. Consistent with this activity, administration of stauprimide inhibited tumor growth in rodent xenograft models. Our study provides a unique strategy for selectively targeting MYC transcription by pharmacological means as a potential treatment for MYCdependent tumors.MYC | stauprimide | NME2 | nuclear localization | cancer T he transcription factor MYC participates in diverse cellular processes by regulating the transcription of a large number of genes involved in gene expression, cell division, apoptosis, cell adhesion, stem cell self-renewal and differentiation, and metabolism (1-3). MYC is an oncogene whose expression is elevated in up to 75% of all cancers with various tissue origins (4); MYC expression levels also correlate with prognostic outcomes in patients of various types of malignancies (5, 6). In addition to its well-established roles in tumor initiation and cancer cell survival and proliferation, MYC has been shown to be involved in tumor microenvironment remodeling, drug resistance, and cancer stem cell maintenance (7-9). Recent studies have also revealed a role for MYC in regulating the transcription of immune checkpoint genes, including CD47 and PD-L1 in cancer cells, suggesting that MYC is involved in cancer escape from immune surveillance (10).Overexpression of MYC is able to induce malignant transformation in skin (11), lung (12), liver (13), breast (14, 15), and hematopoietic cells (16) in transgenic mouse models, and termination of MYC overexpression results in halted cancer cell proliferation, increased apoptosis and terminal differentiation, and tumor regression. Furthermore, inhibition of endogenous MYC by the inducible expression of a dominant-negative variant of MYC, Omomyc, is able to induce tumor regression in transgenic mouse models of lung cancer (17). More intriguingly, transient deactivation of MYC overexpression (18) and episodic expression of Omomyc (19) have been shown to induce irreversible tumor regression in osteosarcoma and lung cancer transgenic mouse models, suggesting the potential of MYCtargeted anticancer therapies.Drug discovery efforts have attempted to directly and indirectly modulate MYC-dependent transcription. For example, compounds have been identified that disrupt the interaction between MYC and its transcriptional partner MAX to suppress downstream gene transcription (20)(21)(22)(23)(2...

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Nm23-M2/NDP kinase B induces endogenous c-myc and nm23-M1/NDP kinase A overexpression in BAF3 cells. Both NDP kinases protect the cells from oxidative stress-induced death

Cited by 33 publications

References 34 publications

Plakoglobin interacts with and increases the protein levels of metastasis suppressor Nm23-H2 and regulates the expression of Nm23-H1

Plakoglobin interacts with and increases the protein levels of metastasis suppressor Nm23-H2 and regulates the expression of Nm23-H1

Proteome analyses of the growth inhibitory effects of NCH-51, a novel histone deacetylase inhibitor, on lymphoid malignant cells

Small molecule selectively suppresses MYC transcription in cancer cells

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