Xingguo Liu
Siim Pauklin
1 Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences Old Road, University of Oxford, Oxford OX3 7LD, UK;
2 Guangzhou Regenerative Medicine and Health Guangdong Laboratory, CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences;
Guangzhou Medical University, Guangzhou 510530, China;
3 Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Institute for Stem Cell and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
Funds: Royal Society, UK
Work in S.P.'s laboratory is supported by a Cancer Research UK Career Development Fellowship, Grant ID C59392/A25064
and The Clarendon Fund and St Edmund Hall Scholarship, UK, SFF1920_CB_MSD_759707.
Received Date: 2020-08-07
Rev Recd Date:2020-12-05
Abstract
Abstract
Dedifferentiation of cell identity to a progenitor-like or stem cell-like state with increased cellular plasticity is frequently observed in cancer formation. During this process, a subpopulation of cells in tumours acquires a stem cell-like state partially resembling to naturally occurring pluripotent stem cells that are temporarily present during early embryogenesis. Such characteristics allow these cancer stem cells (CSCs) to give rise to the whole tumour with its entire cellular heterogeneity and thereby support metastases formation while being resistant to current cancer therapeutics. Cancer development and progression are demarcated by transcriptional dysregulation. In this article, we explore the epigenetic mechanisms shaping gene expression during tumorigenesis and cancer stem cell formation, with an emphasis on 3D chromatin architecture. Comparing the pluripotent stem cell state and epigenetic reprogramming to dedifferentiation in cellular transformation provides intriguing insight to chromatin dynamics. We suggest that the 3D chromatin architecture could be used as a target for re-sensitizing cancer stem cells to therapeutics.Keywords: chromatin architecture,
3D chromatin topology,
epigenetics,
tumorigenesis,
cancer stem cells,
pluripotent stem cells
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