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Epigenome analysis of PDAC cancer stem cells and non-cancer stem cells

ABSTRACT: Most carcinomas, including pancreatic ductal adenocarcinoma (PDAC), are hierarchically organized with cancer stem cells (CSCs) residing at the top of the hierarchy and driving tumor progression, metastasis, and chemoresistance. Since CSCs and their more differentiated progenies (non-CSCs) share an identical genetic background, differences in epigenetics should account for the striking functional differences between these two populations of cells. Epigenetic mechanisms, such as DNA methylation, play an important role in maintaining pluripotency and regulating the differentiation of stem cells, but the role of DNA methylation in pancreatic CSCs remains unclear. Therefore, the objective of our study was to investigate the genome-wide DNA methylation profile of PDAC CSCs and to determine the importance of DNMT methyltransferases for CSC maintenance and tumorigenicity. Using high-throughput methylation analysis, we discovered that sorted CSCs have a higher level of DNA methylation, regardless of the heterogeneity or polyclonality of the CSC populations present in the tumors analyzed. Mechanistically, CSCs expressed higher DNMT1 levels than non-CSCs, and pharmacological or genetic targeting of DNMT1 in CSCs reduced their self-renewal and in vivo tumorigenic potential, highlighting DNMT1 as a potentially attractive therapeutic target.

ORGANISM(S): Homo sapiens

PROVIDER: GSE80241 | GEO | 2017/04/12

SECONDARY ACCESSION(S): PRJNA318383

REPOSITORIES: GEO

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Pancreatic ductal adenocarcinoma primary cultures enriched or not in cancer stem cells

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