Aberrant DNA methylation of integrin α4: a potential novel role for metastasis of cholangiocarcinoma

Uhm, Kyung Ok; Lee, Jung Ok; Lee, Yun Mi; Lee, Eun Soo; Kim, Hyeon Soo; Park, Sun Hwa

doi:10.1007/s00432-009-0646-9

Cited by 19 publications

(10 citation statements)

References 29 publications

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“…A similar complex regulation of gene expression was shown for another member of the same integrin subfamily integrin alpha4beta1-aberrant DNA methylation of its promoter region results in integrin alpha4 silencing in 55% of cholangiocarcinomas, 38 84.7% of 46 primary gastric tumors and 8 of 9 gastric cancer cell lines 39 while TSA treatment upregulated integrin alpha4 expression in hepatocellular carcinoma cell line Hep3B. 40 The obtained data show complexity of ITGA9 regulation in breast cancer cells that result in existence of ITGA9-expressing or ITGA9-non-expressing breast tumors.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 90%

Integrin alpha9 (ITGA9) expression and epigenetic silencing in human breast tumors

Mostovich¹,

Prudnikova²,

Kondratov

et al. 2011

Cell Adhesion & Migration

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Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 90%

Integrin alpha9 (ITGA9) expression and epigenetic silencing in human breast tumors

Mostovich¹,

Prudnikova²,

Kondratov

et al. 2011

Cell Adhesion & Migration

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“…DNA hypermethylation leads to the downregulation and silencing of tumor suppressor genes during the pathogenesis of various human cancers [10,34-36]. Recently, genome-wide array-based studies have reported altered DNA methylation gene profiles in CRC [22-24].…”

Section: Discussionmentioning

confidence: 99%

Identification of novel hypermethylated genes and demethylating effect of vincristine in colorectal cancer

Moon

Lee

et al. 2014

J Exp Clin Cancer Res

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BackgroundColorectal cancer (CRC) arises as a consequence of genetic events such as gene mutation and epigenetic alteration. The aim of this study was to identify new hypermethylated candidate genes and methylation-based therapeutic targets using vincristine in CRC.MethodsWe analyzed the methylation status of 27,578 CpG sites spanning more than 14,000 genes in CRC tissues compared with adjacent normal tissues and normal colon tissues using Illumina bead chip array. Twenty-one hypermethylated genes and 18 CpG island methylator phenotype markers were selected as candidate genes. The methylation status of 39 genes was validated by quantitative methylation-specific polymerase chain reaction in CRC tissues, adjacent normal tissues, normal colon cells, and three CRC cell lines. Of these, 29 hypermethylated candidate genes were investigated using the demethylating effects of 5-aza-2′-deoxycytidine (5-aza-dC) and vincristine in CRC cells.ResultsThirty-two out of 39 genes were hypermethylated in CRC tissues compared with adjacent normal tissues. Vincristine induced demethylation of methylated genes in CRC cells to the same extent as 5-aza-dC. The mRNA expression of AKR1B1, CHST10, ELOVL4, FLI1, SOX5, STK33, and ZNF304 was restored by treatment with 5-aza-dC and vincristine.ConclusionThese results suggest that these novel hypermethylated genes AKR1B1, CHST10, ELOVL4, SOX5, STK33, and ZNF304 may be potential methylation biomarkers and therapeutic targets of vincristine in CRC.

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“…Interestingly, α (2)-integrin has been described to play a crucial role in hepatocarcinoma cell invasion and metastasis [30], while a transcriptional repression of the integrin α 4 gene caused by aberrant DNA methylation has been demonstrated in gastric cancer and cholangiocarcinoma [31]. …”

Section: Resultsmentioning

confidence: 99%

Role of Tumor Associated Fibroblasts in Human Liver Regeneration, Cirrhosis, and Cancer

Cesselli

Beltrami

Poz

et al. 2011

International Journal of Hepatology

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Tumor associated fibroblasts (TAFs) are considered a microenvironmental element critical for tumor growth and progression. Experimental studies suggest that their origin could be from mesenchymal stem cells (MSCs) derived from the bone marrow. However, the role played by TAFs in cirrhosis, hepatocellular carcinoma development, and progression is largely unknown, and in vitro human models are missing. This paper for the first time demonstrates that (1) human neoplastic livers possess a population of multipotent adult stem cells (MASCs) with properties of TAFs; (2) a population of MASC-derived TAFs is already present in cirrhotic, not yet neoplastic, livers; (3) MASCs isolated from nonneoplastic and noncirrhotic liver scan acquire a TAF phenotype when grown in a medium conditioned by tumor cell lines, supporting the notion that TAF could originate from resident primitive cells (MASCs), possibly through a paracrine mechanism.

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Aberrant DNA methylation of integrin α4: a potential novel role for metastasis of cholangiocarcinoma

Abstract: Taken together, these results suggest that loss of the integrin alpha4 gene is caused by aberrant DNA methylation of the 5'-CpG island site of the gene, and methylation of the integrin alpha4 gene can be a useful marker of metastasis of CC.

Cited by 19 publications

References 29 publications

Integrin alpha9 (ITGA9) expression and epigenetic silencing in human breast tumors

Integrin alpha9 (ITGA9) expression and epigenetic silencing in human breast tumors

Identification of novel hypermethylated genes and demethylating effect of vincristine in colorectal cancer

Role of Tumor Associated Fibroblasts in Human Liver Regeneration, Cirrhosis, and Cancer

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