Article

Expression of histone deacetylase 1 and metastasis-associated protein 1 as prognostic factors in colon cancer.

Department of Surgery, Institute of Health Biosciences, The University of Tokushima, Tokushima 770-8503, Japan.
Oncology Reports (impact factor: 1.84). 08/2011; 26(2):343-8. DOI:10.3892/or.2011.1312 pp.343-8
Source: PubMed

ABSTRACT Histone deacetylase 1 (HDAC1) and metastasis-associated protein 1 (MTA1) form the nucleosome remodeling and histone deacetylation (NuRD) complex and may possibly play a central role in cancer development. However, limited data has been reported regarding the expression of both HDAC1 and MTA1. The aim of the present study was to clarify the clinical role of HDAC1 and MTA1 expression in colon cancer. Seventy-four patients with colon cancer, who underwent colectomy at our institution, were enrolled in this study. Expression of HDAC1 and MTA1 was examined immunohistochemically. The patients were divided into four groups: HDAC1-positive group (n=58), HDAC1-negative group (n=16), MTA1-positive group (n=38) and MTA1-negative group (n=36). Clinicopathological factors and survival rates were compared between the groups. Regarding the clinicopathological factors, the depth of tumor invasion and stage correlated significantly with HDAC1 expression (p<0.05). Age, depth of tumor invasion and vascular invasion tended to correlate with MTA1 expression. The 5-year survival rate in the HDAC1-positive group (55.1%) was significantly worse compared to the HDAC1-negative group (86.5%) (p<0.05), and the 5-year survival rate of the MTA1-positive group (50.5%) was significantly worse than that of the MTA1-negative group (73.1%) (p=0.05). In patients with stages II-IV and curability A, B, the survival rate in those with HDAC1-positive expression was significantly worse than those with HDAC1-negative expression (p<0.05), and the survival rate of the MTA1-positive group tended to be worse than that of the MTA1-negative group (p=0.07). Overall survival in both the HDAC1 and MTA1-positive groups was significantly worse than overall survival of the other groups (p<0.05). Disease-free survival in both the HDAC1- and MTA1-positive groups, among patients with stages II-IV and curability A, B, was also significantly worse than that of the other groups (p<0.05). HDAC1 and MTA1 expression levels were significantly related to poorer prognosis. Therefore, HDAC1 and MTA1 expression levels are potential prognostic indicators for colon cancer.

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    Article: MTA-1 expression is associated with metastasis and epithelial to mesenchymal transition in colorectal cancer cells.
    Seda Tuncay Cagatay, Ismail Cimen, Berna Savas, Sreeparna Banerjee
    [show abstract] [hide abstract]
    ABSTRACT: Although metastasis associated protein 1 (MTA1) has been widely linked to tumor metastasis, the relevant mechanisms remain to be elucidated, especially in colorectal cancer (CRC). Here, we have investigated the link between MTA1, metastasis and epithelial-mesenchymal transition (EMT) in CRC. Eighteen normal colon tissues and 91 resected tumor samples were analyzed for MTA1 expression by immunohistochemistry (IHC). IHC indicated low or no nuclear MTA1 expression in the normal tissues and significantly higher expression in Grade II, Grade III and liver metastasis tumors. No statistically significant difference was observed in MTA1 expression between Grade III and liver metastatic tumors. To demonstrate the functional importance of MTA1 in vitro, the gene was silenced in HCT-116 cells and LoVo cells and overexpressed in HCT-116 cells. MTA1 overexpression in HCT-116 cells enhanced proliferation, adhesion to fibronectin, motility, migration, invasion through Matrigel, anchorage-independent growth, neoangiogenesis and induced a loss of apoptosis. Silencing of MTA1 resulted in a reversal of all of these features. Mechanistically, MTA1 silencing caused an increase in the epithelial markers E-cadherin and ZO-1 and a decrease in the mesenchymal marker vimentin while MTA1 overexpression caused an increase in vimentin expression. Moreover, MTA1 enhanced the expression of Snai1 and Slug; silencing of MTA1 reduced their recruitment to the promoter of E-cadherin, thereby leading to its expression. MTA1 is highly expressed in higher grade tumors and is important in the orchestration of various phenotypic changes in CRC, most likely by inducing EMT. This further corroborates its role as a master regulator in tumorigenesis.
    Tumor Biology 01/2013; · 1.94 Impact Factor
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Keywords

5-year survival rate
 
cancer development
 
central role
 
clinical role
 
colon cancer
 
HDAC1 expression
 
HDAC1-negative expression
 
HDAC1-negative group
 
HDAC1-positive expression
 
HDAC1-positive group
 
Histone deacetylase 1
 
histone deacetylation
 
metastasis-associated protein 1
 
MTA1 expression
 
MTA1 expression levels
 
MTA1-negative group
 
MTA1-positive group
 
MTA1-positive groups
 
survival rates
 
tumor invasion