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Adv Exp Med Biol. 2019;1139:115-126. doi: 10.1007/978-3-030-14366-4_7.

Heterogeneity of Colon Cancer Stem Cells.

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Division of Animal Experiment, Life Science Research Center, Gifu University, Gifu City, Gifu, Japan.
Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu City, Gifu, Japan.
Medical Science Division, United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu City, Gifu, Japan.
Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu City, Gifu, Japan.


Colorectal cancer (CRC) remains the fourth leading cause of cancer death worldwide. Cancer stem cells (CSCs) have attracted a great deal of interest because of their potential clinical implications in a range of cancers, including CRC. CSCs were initially considered to be cell populations with well-defined phenotypic and molecular characteristics. However, accumulating evidence suggests that CSCs represent a phenotypically and functionally heterogeneous population. Recent studies also demonstrate colorectal CSCs to be dynamic rather than static populations that are continuously altered by various extrinsic factors in addition to intrinsic cellular factors such as genetic and epigenetic alterations. Thus, CSCs do not represent a fixed target population any longer, and their heterogeneous and dynamic nature present a serious problem in establishing specific therapeutic strategies. This chapter summarizes past and current literature related to CSC population heterogeneity and dynamics in CRC tissues, including evidence of the presence of distinct CSC subpopulations and signaling pathways and intra- and extra-tumoral factors involved in the regulation of CSCs in cancer tissues.


Cancer stem cell; Cancer stem cell marker; Colorectal cancer; Heterogneity; Intestinal stem cell; Metastasis; Plasticity; Reversion; Tumor microenvironment; Wnt signaling

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