A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA291636 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Cancer invasion and metastasis is the most morbid aspect of cancer and is governed by different cellular mechanisms than those driving the deregulated growth of tumors. We addressed here the question of whether a common DNA methylation signature of invasion exists in cancer cells from different origins that differentiates invasive from noninvasive cells. We identified a common DNA methylation signature consisting of hyper- and hypomethylation and determined the overlap of differences in DNA methylation with differences in mRNA expression using expression array analyses. A pathway analysis reveals that the hypomethylation signature includes some of the major pathways that were previously implicated in cancer migration and invasion such as TGF beta and ERBB2 triggered pathways. The relevance of these hypomethylation events in human tumors was validated by identification of the signature in several publicly available databases of human tumor transcriptomes. We shortlisted novel invasion promoting candidates and tested the role of four genes from the list C11orf68, G0S2, SHISA2 and TMEM156 in invasiveness using siRNA depletion. Importantly these genes are upregulated in human cancer specimens as determined by immunostaining of human normal and cancer breast, liver and prostate tissue arrays. Since these genes are activated in cancer they constitute a group of targets for specific pharmacological inhibitors of cancer invasiveness. Our study provides evidence that common DNA hypomethylation signature exists between cancer cells derived from different tissues, pointing to a common mechanism of cancer invasiveness in cancer cells from different origins.
2017-02-09 | GSE71626 | GEO
Project description:Cancer invasion and metastasis is the most morbid aspect of cancer and is governed by different cellular mechanisms than those driving the deregulated growth of tumors. We addressed here the question of whether a common DNA methylation signature of invasion exists in cancer cells from different origins that differentiates invasive from noninvasive cells. We identified a common DNA methylation signature consisting of hyper- and hypomethylation and determined the overlap of differences in DNA methylation with differences in mRNA expression using expression array analyses. A pathway analysis reveals that the hypomethylation signature includes some of the major pathways that were previously implicated in cancer migration and invasion such as TGF beta and ERBB2 triggered pathways. The relevance of these hypomethylation events in human tumors was validated by identification of the signature in several publicly available databases of human tumor transcriptomes. We shortlisted novel invasion promoting candidates and tested the role of four genes from the list C11orf68, G0S2, SHISA2 and TMEM156 in invasiveness using siRNA depletion. Importantly these genes are upregulated in human cancer specimens as determined by immunostaining of human normal and cancer breast, liver and prostate tissue arrays. Since these genes are activated in cancer they constitute a group of targets for specific pharmacological inhibitors of cancer invasiveness. Our study provides evidence that common DNA hypomethylation signature exists between cancer cells derived from different tissues, pointing to a common mechanism of cancer invasiveness in cancer cells from different origins.
2017-02-09 | GSE71625 | GEO
Project description:Cancer invasion and metastasis is the most morbid aspect of cancer and is governed by different cellular mechanisms than those driving the deregulated growth of tumors. We addressed here the question of whether a common DNA methylation signature of invasion exists in cancer cells from different origins that differentiates invasive from non-invasive cells. We identified a common DNA methylation signature consisting of hyper- and hypomethylation and determined the overlap of differences in DNA methylation with differences in mRNA expression using expression array analyses. A pathway analysis reveals that the hypomethylation signature includes some of the major pathways that were previously implicated in cancer migration and invasion such as TGF beta and ERBB2 triggered pathways. The relevance of these hypomethylation events in human tumors was validated by identification of the signature in several publicly available databases of human tumor transcriptomes. We shortlisted novel invasion promoting candidates and tested the role of four genes in cellular invasiveness from the list C11orf68, G0S2, SHISA2 and TMEM156 in invasiveness using siRNA depletion. Importantly these genes are upregulated in human cancer specimens as determined by immunostaining of human normal and cancer breast, liver and prostate tissue arrays. Since these genes are activated in cancer they constitute a group of targets for specific pharmacological inhibitors of cancer invasiveness.Our study provides evidence that common DNA hypomethylation signature exists between cancer cells derived from different tissues, pointing to a common mechanism of cancer invasiveness in cancer cells from different origins that could serve as drug targets.
| S-EPMC4741763 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-02-09 | GSE71627 | GEO
Project description:Extensive loss of DNA methylation is a hallmark of cancer. The role of hypomethylation in altering gene expression in cancer cells has been poorly understood. Hepatic cellular carcinoma (HCC) is one of the most common human cancers. We use HCC as a model to investigate hypomethylation in cancer by a combination of methylated DNA immunoprecipitation and hybridization with comprehensive promoter arrays. We identify approximately 2,800 promoters that are hypomethylated in tumor samples. The hypomethylated promoters appear in clusters across the genome suggesting a high-level organization behind the epigenomic changes in cancer. The genes whose promoters are demethylated are mainly involved in cell growth, cell adhesion and communication, signal transduction, mobility and invasion; functions that are essential for cancer progression and metastasis. Previous studies suggested that MBD2 was involved in demethylation of uPA and MMP2 genes in human breast and prostate cancer cell lines. We extend these results here showing that whereas MBD2 depletion in normal liver cells has little or no effect, its depletion in the human hepatocellular carcinoma cell line HepG2 and the adenocarcinoma cell line SkHep1 results in suppression of cell growth, anchorage-independent growth and invasiveness, as well as an increase in promoter methylation and silencing of several of the genes that are hypomethylated in tumors. Our studies establish for the first time the rules governing hypomethylation of promoters in liver cancer and define the potential functional role of hypomethylation in cancer. Cancerous and normal adjacent tissue samples were obtained from 11 patients with HCC from the Chinese National Human Genome Center at Shanghai, China (Dr. Ze-Guang Han). For three patients, the cancer samples were dissected using the laser capture microdissection technique. Gene expression profiles for these patients were generated using Affymetrix expression microarrays.
2011-06-04 | E-GEOD-29721 | biostudies-arrayexpress
Project description:Extensive loss of DNA methylation is a hallmark of cancer. The role of hypomethylation in altering gene expression in cancer cells has been poorly understood. Hepatic cellular carcinoma (HCC) is one of the most common human cancers. We use HCC as a model to investigate hypomethylation in cancer by a combination of methylated DNA immunoprecipitation and hybridization with comprehensive promoter arrays. We identify approximately 2,800 promoters that are hypomethylated in tumor samples. The hypomethylated promoters appear in clusters across the genome suggesting a high-level organization behind the epigenomic changes in cancer. The genes whose promoters are demethylated are mainly involved in cell growth, cell adhesion and communication, signal transduction, mobility and invasion; functions that are essential for cancer progression and metastasis. Previous studies suggested that MBD2 was involved in demethylation of uPA and MMP2 genes in human breast and prostate cancer cell lines. We extend these results here showing that whereas MBD2 depletion in normal liver cells has little or no effect, its depletion in the human hepatocellular carcinoma cell line HepG2 and the adenocarcinoma cell line SkHep1 results in suppression of cell growth, anchorage-independent growth and invasiveness, as well as an increase in promoter methylation and silencing of several of the genes that are hypomethylated in tumors. Our studies establish for the first time the rules governing hypomethylation of promoters in liver cancer and define the potential functional role of hypomethylation in cancer.
2011-06-04 | GSE29721 | GEO
Project description:Extensive loss of DNA methylation is a hallmark of cancer. The role of hypomethylation in altering gene expression in cancer cells has been poorly understood. Hepatic cellular carcinoma (HCC) is one of the most common human cancers. We use HCC as a model to investigate hypomethylation in cancer by a combination of methylated DNA immunoprecipitation and hybridization with comprehensive promoter arrays. We identify approximately 2,800 promoters that are hypomethylated in tumor samples. The hypomethylated promoters appear in clusters across the genome suggesting a high-level organization behind the epigenomic changes in cancer. The genes whose promoters are demethylated are mainly involved in cell growth, cell adhesion and communication, signal transduction, mobility and invasion; functions that are essential for cancer progression and metastasis. Previous studies suggested that MBD2 was involved in demethylation of uPA and MMP2 genes in human breast and prostate cancer cell lines. We extend these results here showing that whereas MBD2 depletion in normal liver cells has little or no effect, its depletion in the human hepatocellular carcinoma cell line HepG2 and the adenocarcinoma cell line SkHep1 results in suppression of cell growth, anchorage-independent growth and invasiveness, as well as an increase in promoter methylation and silencing of several of the genes that are hypomethylated in tumors. Our studies establish for the first time the rules governing hypomethylation of promoters in liver cancer and define the potential functional role of hypomethylation in cancer.
2011-06-04 | GSE29720 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE29720: The landscape of promoter DNA hypomethylation in liver cancer (MeDIP-chip data) GSE29721: The landscape of promoter DNA hypomethylation in liver cancer (expression data) Refer to individual Series
2011-06-04 | E-GEOD-29722 | biostudies-arrayexpress
Project description:Extensive loss of DNA methylation is a hallmark of cancer. The role of hypomethylation in altering gene expression in cancer cells has been poorly understood. Hepatic cellular carcinoma (HCC) is one of the most common human cancers. We use HCC as a model to investigate hypomethylation in cancer by a combination of methylated DNA immunoprecipitation and hybridization with comprehensive promoter arrays. We identify approximately 2,800 promoters that are hypomethylated in tumor samples. The hypomethylated promoters appear in clusters across the genome suggesting a high-level organization behind the epigenomic changes in cancer. The genes whose promoters are demethylated are mainly involved in cell growth, cell adhesion and communication, signal transduction, mobility and invasion; functions that are essential for cancer progression and metastasis. Previous studies suggested that MBD2 was involved in demethylation of uPA and MMP2 genes in human breast and prostate cancer cell lines. We extend these results here showing that whereas MBD2 depletion in normal liver cells has little or no effect, its depletion in the human hepatocellular carcinoma cell line HepG2 and the adenocarcinoma cell line SkHep1 results in suppression of cell growth, anchorage-independent growth and invasiveness, as well as an increase in promoter methylation and silencing of several of the genes that are hypomethylated in tumors. Our studies establish for the first time the rules governing hypomethylation of promoters in liver cancer and define the potential functional role of hypomethylation in cancer. Cancerous and normal adjacent tissue samples were obtained from 11 patients with HCC from the Chinese National Human Genome Center at Shanghai, China (Dr. Ze-Guang Han). For three patients, the cancer samples were dissected using laser capture microdissection technique. All patients provided written informed consent, and the Ethics Committee from the Chinese National Human Genome Center at Shanghai approved all aspects of this study. Human HCC HepG2 cells and adenocarcinoma SkHep1 cells were purchased from ATCC (HB8065 and HTB52, respectively, USA), whereas human untransformed hepatocytes (normal hepatocytes, NorHep) were obtained from Celprogen (33003-02, USA). Purified DNA from cancerous samples and normal adjacent samples, as well as HepG2 and NorHep cells, was enriched for methylated DNA using the MeDIP protocol developed by Cedar's group (PMID 16444255). The labeled input and bound DNA samples were hybridized to a custom-designed 244K promoter tiling array that contained probes covering all transcription start sites at intervals from 800 bp upstream to 200 bp downstream of all genes described in Ensembl (version 44) and within 250 bp of the ~400 microRNAs from miRBase, all at 100 bp-spacing.
2011-06-04 | E-GEOD-29720 | biostudies-arrayexpress
Project description:The landscape of promoter DNA hypomethylation in liver cancer
| PRJNA141097 | ENA