Identification of the Tumor Metastasis Suppressor Nm23-H1/Nm23-R1 as a Constituent of the Centrosome

Roymans, Dirk; Vissenberg, Kris; Jonghe, Chris De; Willems, Roel; Engler, Gilbert; Kimura, Narimichi; Grobben, Bert; Claes, Patrik; Verbelen, Jean‐Pierre; Broeckhoven, Christine Van; Slegers, Herman

doi:10.1006/excr.2000.5087

Cited by 39 publications

(27 citation statements)

References 37 publications

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“…The expression of Nm23-H5 is testis is contract to Nm23-H1 and Nm23-H4 expression is depends upon the tissue. Nm23-H6 isoform (house keeping gene) are mitochondrial enzymes involves in conserve intracellular levels of NTP at the expense of ATP (Venturelli et al, 2000;Roymans et al, 2001). In addition to Nm23 family a neoteric protein Nm23-LV are overall expressed and encodes a protein consisting of the major part of Nm23-H1 and Nm23-H2 amino acids (Valentijn et al, 2006).…”

Section: Nm23 Gene Family Isoformsmentioning

confidence: 99%

Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

Prabhu

Siddikuzzaman²,

Grace³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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The Nm23 gene is a metastatic suppressor identified in a melanoma cell line and expressed in different tumors where their levels of expression are associated with reduced or increased metastatic potential. Nm23 is one of the over 20 metastasis suppressor genes (MSGs) confirmed in vivo. It is highly conserved from yeast to human, implying a critical developmental function. Tumors with alteration of the p53 gene and reduced expression of the Nm23 gene are more prone to metastasis. Nm23-H1 has 3'-5' exonuclease activity. This review focuses on the role of Nm23 in cancer progression and also a potential novel target for cancer therapy.

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Section: Nm23 Gene Family Isoformsmentioning

confidence: 99%

Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

Prabhu

Siddikuzzaman²,

Grace³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…Given that NDP kinase co-localizes partially with the microtubular network in epithelial cells (Pinon et al, 1999) and the centrosome of C6 glioma cells (Roymans et al, 2001), we investigated the relationship between microtubules and the vesicles coated with NDP kinase by double labeling with antibodies to α-tubulin and NDP kinase (Fig. 9).…”

Section: Characterization Of the Vesicles Labeled By Ndp Kinasementioning

confidence: 99%

“…NDP kinase co-immunoprecipitates from cell lysates with tubulin (Lombardi et al, 1995;Roymans et al, 2001) and colocalizes partially with microtubules in intact cells (Pinon et al, 1999), although purified NDP kinase does not bind directly to microtubules (Melki et al, 1992). To determine whether the NDP kinase pool bound to the MT/Ves pellet was associated with tubulin prior to the formation of microtubules, the postnuclear supernatant was centrifuged at 230,000 g to sediment membranes.…”

Section: Characterization Of the Vesicles Labeled By Ndp Kinasementioning

confidence: 99%

Receptor activation regulates cortical, but not vesicular localization of NDP kinase

Gallagher

Parrott

Szabó

et al. 2003

Journal of Cell Science

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We used immunofluorescence techniques to determine the localization of nucleoside diphosphate (NDP) kinase in NIH-3T3 fibroblasts. We found that cytoplasmic NDP kinase can be separated into two populations according to subcellular localization and response to extracellular stimuli. Specifically,within minutes of stimulation of resting fibroblasts with serum, growth factors or bombesin, a portion of NDP kinase becomes associated with membrane ruffles and lamellipodia. Another pool of NDP kinase accumulates independently of stimulation around intracellular vesicles. Transfection of cells with activated Rac mimics, whereas expression of dominant negative Rac inhibits,the effects of extracellular stimulation on the translocation of NDP kinase to the cell cortex. Neither Rac mutant affects the vesicle-associated pool. Association of NDP kinase with vesicles depends on microtubule integrity and is disrupted by nocodazole. In cell-free assays NDP kinase binds tightly to membrane vesicles associated with taxol-stabilized microtubules. Binding of NDP kinase to this fraction is reduced by ATP and abolished by GTP, as well as guanine nucleotides that are NDP kinase substrates. Thus, the localization of the two NDP kinase pools identified here is regulated independently by distinct cellular components: the appearance of cortical NDP kinase is a consequence of Rac activation, whereas vesicular NDP kinase is responsive to microtubule dynamics and nucleotides, in particular GTP. These results suggest that in fibroblasts NDP kinase participates in Rac-related cortical events and in GTP-dependent processes linked to intracellular vesicle trafficking.

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“…Recently, it was reported that increased nm23-H1 expression, induced by an inhibitor of DNA methylation, reduced cell motility but had little e ect on cell proliferation (Hartsough et al, 2001). Other investigators have reported that nm23-H1 may also play a role in the regulation of cell structure and shape, as it has been shown to be a constituent of the centrosome (Roymans et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas–a possible mechanism for altering the nm23-H1 activity

et al. 2001

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PRUNE, the human homologue of the Drosophila gene, is located in 1q21.3, a region highly ampli®ed in human sarcomas, malignant tumours of mesenchymal origin. Prune protein interacts with the metastasis suppressor nm23-H1, but shows impaired a nity towards the nm23-H1 S120G mutant associated with advanced neuroblastoma. Based on these observations, we previously suggested that prune may act as a negative regulator of nm23-H1 activity. We found ampli®cation of PRUNE in aggressive sarcoma subtypes, such as leiomyosarcomas and malignant ®brous histiocytomas (MFH) as well as in the less malignant liposarcomas. PRUNE ampli®cation was generally accompanied by high mRNA and moderate to high protein levels. The sarcoma samples expressed nm23-H1 mostly at low or moderate levels, whereas mRNA and protein levels were moderate to high in breast carcinomas. For the more aggressive sarcoma subtypes, 9/13 patients with PRUNE ampli®cation developed metastases. A similar situation was observed in all breast carcinomas with ampli®cation of PRUNE. Infection of NIH3T3 cells with a PRUNE recombinant retrovirus increased cell proliferation. Possibly, ampli®-cation and overexpression of PRUNE has the same e ect in the tumours. We suggest that ampli®cation and overexpression of PRUNE could be a mechanism for inhibition of nm23-H1 activity that a ect the development or progression of these tumours. Oncogene (2001) 20, 6881 ± 6890.

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Identification of the Tumor Metastasis Suppressor Nm23-H1/Nm23-R1 as a Constituent of the Centrosome

Cited by 39 publications

References 37 publications

Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

Receptor activation regulates cortical, but not vesicular localization of NDP kinase

Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas–a possible mechanism for altering the nm23-H1 activity

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