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Nicolson, Garth L.; Nawa, Akihiro; Toh, Yasushi; Taniguchi, Shigeki; Nishimori, Katsuhiko; Moustafa, Amr Soliman

doi:10.1023/a:1022534217769

Cited by 139 publications

(41 citation statements)

References 37 publications

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“…The MTA1 gene was found to be overexpressed in a variety of cancerous tissues including breast, esophageal, colorectal, gastric and pancreatic carcinomas (Toh et al, 1997(Toh et al, , 1999Iguchi et al, 2000;Nawa et al, 2000a). The MTA1 protein is likely a nuclear regulatory protein, and it might interact with specific genes involved in cellular regulation (Nicolson et al, 2003). Antisense oligonucleotide treatment of breast cancer cell lines that showed high levels of expression of the MTA1 gene inhibited the cell growth and in vitro invasion (Nawa et al, 2000b).…”

Section: Discussionmentioning

confidence: 99%

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Prediction of high risk Ewing's sarcoma by gene expression profiling

et al. 2004

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Ewing's sarcoma (ES) is the second most common primary malignant bone tumor in children and adolescents. Currently accepted clinical prognostic factors fail to classify ES patients' risk to relapse at diagnosis. We aimed to find a new strategy to distinguish between poor and good prognosis ES patients already at diagnosis. We analysed the gene expression profiles of 14 primary tumor specimens and six metastases from ES patients, using oligonucleotide microarray analysis. The over-expression of two genes was validated by quantitative PCR using the LightCycler system. We identified two distinct gene expression signatures distinguishing high-risk ES patients that are likely to progress from low-risk ES patients with a favorable prognosis of long-term progression-free survival. The microarray-based classification was superior to currently used prognostic parameters. Over-expressed genes in the poor prognosis patients included genes regulating the cell cycle and genes associated with invasion and metastasis, while among the downregulated genes were tumor suppressor genes and inducers of apoptosis. Our results indicate the existence of a specific gene expression signature of outcome in ES already at diagnosis, and provide a strategy to select patients who would benefit from risk-adapted improved therapy.

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Section: Discussionmentioning

confidence: 99%

“…Examination of the MTA1 protein suggests that it is a histone deacetylase and may serve multiple functions in cellular signaling, chromosome remodeling and transcription processes that are important in the progression, invasion and growth of metastatic cells (Nicolson et al, 2003).…”

Section: Validation Of Overexpressed Genes By Rq-pcrmentioning

confidence: 99%

Prediction of high risk Ewing's sarcoma by gene expression profiling

et al. 2004

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“…Recent studies have shown that treatment of cells with 5-azacytidine can induce expression of the metastasis suppressor genes Nm23 (44) and KAI1 (45). Links between metastasis and HDAC activity first became apparent when the breast cancer metastasis promoting gene, MTA1, was identified as a component of the NuRD⅐HDAC complex (46,47). MTA1 has subsequently been shown to repress estrogen receptor-dependent transcription in an HDAC-dependent manner (48).…”

Section: Discussionmentioning

confidence: 99%

Breast Cancer Metastasis Suppressor 1 (BRMS1) Forms Complexes with Retinoblastoma-binding Protein 1 (RBP1) and the mSin3 Histone Deacetylase Complex and Represses Transcription

Meehan

Samant

Hopper

et al. 2004

Journal of Biological Chemistry

159

139

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Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis of multiple human and murine cancer cells without inhibiting tumorigenicity. By yeast two-hybrid and co-immunoprecipitation, BRMS1 interacts with retinoblastoma binding protein 1 and at least seven members of the mSin3 histone deacetylase (HDAC) complex in human breast and melanoma cell lines. BRMS1 co-immunoprecipitates enzymatically active HDAC proteins and represses transcription when recruited to a Gal4 promoter in vivo. BRMS1 exists in large mSin3 complex(es) of ϳ1.4 -1.9 MDa, but also forms smaller complexes with HDAC1. Deletion analyses show that the carboxyl-terminal 42 amino acids of BRMS1 are not critical for interaction with much of the mSin3 complex and that BRMS1 appears to have more than one binding point to the complex. These results further show that BRMS1 may participate in transcriptional regulation via interaction with the mSin3⅐HDAC complex and suggest a novel mechanism by which BRMS1 might suppress cancer metastasis.The complex process of cancer cell dissemination and the establishment of secondary foci involves the acquisition of multiple abilities by metastatic cells. For example, blood-borne metastasis requires cells to invade from the primary tumor, enter the circulation, survive transport, arrest at a secondary site, recruit a blood supply, and proliferate at that site (1). The ability to accomplish all of these steps likely involves changes in, and coordinated expression of, a large assortment of genes. Consistent with this notion, several genes, proteins, and pathways have been associated with metastatic progression, including oncogenes, motility factors, and matrix metalloproteinases (1, 2). In addition to metastasis-promoting genes, a new class of molecules called metastasis suppressors has been described (reviewed in Refs. 2-5). By definition, metastasis suppressors inhibit metastasis without blocking primary tumor growth, presumably by inhibiting one or more steps necessary for metastasis. To date, 13 metastasis suppressor genes have been identified that reduce the metastatic ability of cancer cell line(s) in vivo without affecting tumorigenicity, namely breast cancer metastasis suppressor 1 (BRMS1), 1 CRSP3, DRG1, KAI1, KISS1, MKK4, NM23, RhoGDI2, RKIP, SSeCKs, VDUP1, E-cadherin, and TIMPs (reviewed in Refs. 4 and 5).We identified BRMS1 using differential display to compare highly metastatic breast carcinoma cells with related but metastasis-suppressed cells (6). Enforced expression of BRMS1 suppressed metastasis in three animal models, namely human breast (6), murine mammary (7), and human melanoma cells (8). Additionally, BRMS1 mapped to loci in murine (7) and human (6) genomes that had previously been implicated in metastasis control (9). The BRMS1 protein localized to nuclei and restored gap junctional intercellular communication in both breast and melanoma tumor cell lines (8,10,11), but its molecular functions remain to be elucidated.One approach to determine a mechanism of action involves identifying which...

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“…On the basis of the available data discussed briefly in this review, it is very likely that MTA proteins have important and critical roles in the genesis and progression of a wide variety of cancers [74]. MTA1 protein can be thought of as a master co-regulatory molecule, strongly and clearly suggesting the possibility that MTA1 protein (or its gene) could be an excellent molecular target for cancer therapy as well as its use in cancer diagnosis/prognosis.…”

Section: Mta Proteins As New Molecular Targets: Clinical Implicationsmentioning

confidence: 97%

The role of the MTA family and their encoded proteins in human cancers: molecular functions and clinical implications

Toh

Nicolson

2008

Clin Exp Metastasis

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192

191

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MTA (metastasis-associated gene) is a newly discovered family of cancer progression-related genes and their encoded products. MTA1, the first gene found in this family, has been repeatedly reported to be overexpressed along with its protein product MTA1 in a wide range of human cancers. In addition, the expression of MTA1/MTA1 correlates with the clinicopathological properties (malignant properties) of human cancers. MTA proteins are transcriptional co-repressors that function in histone deacetylation and are involved in the NuRD complex, which contains nucleosome remodeling and histone deacetylating molecules. MTA1 expression correlates with tumor formation in the mammary gland. In addition, MTA1 converts breast cancer cells to a more aggressive phenotype by repression of the estrogen receptor (ER) alpha trans-activation function through deacetylation of the chromatin in the ER-responsive element of ER-responsive genes. Furthermore, MTA1 plays an essential role in c-MYC-mediated cell transformation. Another member of this family, MTA3, is induced by estrogen and represses the expression of the transcriptional repressor Snail, a master regulator of "epithelial to mesenchymal transitions", resulting in the expression of the cell adhesion molecule E-cadherin and maintenance of a differentiated, normal epithelial phenotype in breast cells. In addition, tumor suppressor p53 protein is deacetylated and inactivated by both MTA1 and MTA2, leading to inhibition of growth arrest and apoptosis. Moreover, a hypoxia-inducible factor-1alpha (HIF-1alpha) is also deacetylated and stabilized by MTA1, resulting in angiogenesis. Thus, MTA proteins, especially MTA1, represent a possible set of master co-regulatory molecules involved in the carcinogenesis and progression of various malignant tumors. MTA proteins are proposed to be important new tools for clinical application in cancer diagnosis and treatment.

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Cited by 139 publications

References 37 publications

Prediction of high risk Ewing's sarcoma by gene expression profiling

Prediction of high risk Ewing's sarcoma by gene expression profiling

Breast Cancer Metastasis Suppressor 1 (BRMS1) Forms Complexes with Retinoblastoma-binding Protein 1 (RBP1) and the mSin3 Histone Deacetylase Complex and Represses Transcription

The role of the MTA family and their encoded proteins in human cancers: molecular functions and clinical implications

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