Identification of a DNA methylation signature in CD133+ liver cancer cell lines and its relation with the transforming growth factor beta signaling pathway
type: Dataset
description: Distinct subpopulations of neoplastic cells within tumors, including hepatocellular carcinoma (HCC), display a pronounced ability to initiate new tumors and induce metastasis. Investigations on theses cells rapidly described them as essential for tumor growth and based on theses observations they have been named “cancer stem cells” (CSCs). Unfortunately, the mechanisms involved in sustaining their programs are only partially known. In HCC, there is an established link between microenvironmental signals from Transforming Growth Factor beta (TGF-ß) and survival of certain cell subpopulations which is results in a bad prognosis. However, how TGF-ß establishes and modifies cell behavior in HCC is not fully understood. As DNA methylation is involved in establishing cellular programs, our aim was to characterize the methylome of putative liver CSCs, and its link to the ability of TGF-ß to induce liver CSCs. We used CD133 expression as a positive marker for liver CSC. To understand the relevance of DNA methylation programs in liver CSCs, we first defined the methylome signature of CD133+ cells in liver cancer cells using methylation bead arrays. Differentially methylated CpG sites were enriched in known pathways related to CSC survival and to inflammation, including the TGF-ß/SMAD pathway. Next, we showed that TGF-ß persistently induces CD133+ cells in opposition to another cytokine related to HCC, interleukin 6. We observed that this increase is associated with genome-wide changes in the methylome induced by TGF-ß and that are perpetuated through cell division. We observed a significant overlap between the CD133+ methylome and the methylome induced by TGF-β, indicating that TGF-ß may induce CSC phenotype through DNA methylation reprogramming. Additionally, we observed genome-wide effects of TGF-ß that are independent of the induction of CD133. Finally, TGF-ß methyl-sensitive sites were significantly concentrated in enhancer regions of the genome, and include well-known ta…
landing page: https://theses.hal.science/tel-00942762
identifier: NNT: 2013ENSL0862
keyword: cancer-stem-cells
keyword: carcinome-hepatocelllulaire
keyword: cd133
keyword: cellules-souches-cancereuses
keyword: dna-methylation
keyword: hepatocellular-carcinoma
keyword: infoeu-reposemanticsdoctoralthesis
keyword: methylation-de-ladn
keyword: sdvbclife-sciences-q-biocellular-biology
keyword: sdvcanlife-sciences-q-biocancer
keyword: tgf-beta
keyword: tgfb-pathway
keyword: theses
issued: 2026-05-07T02:28:38.571886
modified: 2026-05-07T02:28:38.571891
language: en
contact point: Organization
  fn: CCSD

test_moissonnage_selune
type: Agent

Identification of a DNA methylation signature in CD133+ liver cancer cell lines and its relation with the transforming growth factor beta signaling pathway
type: Distribution
format: HTML
access URL: https://theses.hal.science/tel-00942762
issued: 2026-05-07T02:28:38.575435
modified: 2026-05-07T02:28:38.558191