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A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness

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 orig...

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Autores principales: Cheishvili, David, Stefanska, Barbara, Yi, Cao, Li, Chen Chen, Yu, Patricia, Arakelian, Ani, Tanvir, Imrana, Khan, Haseeb Ahmed, Rabbani, Shafaat, Szyf, Moshe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741763/
https://www.ncbi.nlm.nih.gov/pubmed/26427334
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author Cheishvili, David
Stefanska, Barbara
Yi, Cao
Li, Chen Chen
Yu, Patricia
Arakelian, Ani
Tanvir, Imrana
Khan, Haseeb Ahmed
Rabbani, Shafaat
Szyf, Moshe
author_facet Cheishvili, David
Stefanska, Barbara
Yi, Cao
Li, Chen Chen
Yu, Patricia
Arakelian, Ani
Tanvir, Imrana
Khan, Haseeb Ahmed
Rabbani, Shafaat
Szyf, Moshe
author_sort Cheishvili, David
collection PubMed
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. SUMMARY: 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.
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spelling pubmed-47417632016-03-11 A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness Cheishvili, David Stefanska, Barbara Yi, Cao Li, Chen Chen Yu, Patricia Arakelian, Ani Tanvir, Imrana Khan, Haseeb Ahmed Rabbani, Shafaat Szyf, Moshe Oncotarget Research Paper 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. SUMMARY: 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. Impact Journals LLC 2015-09-22 /pmc/articles/PMC4741763/ /pubmed/26427334 Text en Copyright: © 2015 Cheishvili et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Cheishvili, David
Stefanska, Barbara
Yi, Cao
Li, Chen Chen
Yu, Patricia
Arakelian, Ani
Tanvir, Imrana
Khan, Haseeb Ahmed
Rabbani, Shafaat
Szyf, Moshe
A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness
title A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness
title_full A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness
title_fullStr A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness
title_full_unstemmed A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness
title_short A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness
title_sort common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741763/
https://www.ncbi.nlm.nih.gov/pubmed/26427334
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