GSE127828 Dynamic imbalance between cancer cell subpopulations induced by Transforming Growth Factor Beta (TGF- β) is associated with a DNA methylome switch [methylation]

Contributor : Hector Hernandez-VargasSeries Type : Methylation profiling by genome tiling arrayOrganism : Homo sapiensDistinct subpopulations of neoplastic cells within tumors, including hepatocellular carcinoma (HCC), display pronounced ability to initiate new tumors and induce metastasis. Recent evidence suggests that signals from transforming growth factor beta (TGF- β) may increase the survival of these so called tumor initiating cells leading to poor HCC prognosis. However, how TGF-β establishes and modifies the key features of these cell subpopulations is not fully understood. In the present report we describe the differential DNA methylome of CD133-negativ e and CD133-expressing liver cancer cells. Next, we show that TGF-β is able to increase the proportion of CD133+ cells in liver cancer cell lines in a way that is stable and persistent across cell division. This process is associated with stable genome-wide changes in DNA methylation that persist t hrough cell division. Differential methylation in response to TGF-β is under-represented at promoter CpG islands and enriched at gene bodies, including a locus in the body of the de novo DNA methyl-transferase DNMT3B gene. Moreover, phenotypic changes induced by TGF-β, including the induction of C D133, are impaired by siRNA silencing of de novo DNA methyl-transferases. Our study reveals a self-perpetuating crosstalk between TGF-β signaling and the DNA methylation machinery, which can be relevant in the establishme...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by genome tiling array Homo sapiens Source Type: research