Principles of stem cell biology and cancer: future applications and therapeutics. Edited by T. Regad, T. J. Sayers and R. C. Rees. John Wiley & Sons (2015)

Part II. Cancer stem cells

The atypical homeobox-only protein (Hopx) has been reported to play a critical role in the differentiation of several cell lineages, including lung alveolar cells, keratinocytes, T cells and trophoblasts (Yamashita et al., 2013). Although not exclusively expressed at this cell position, Hopx has been proposed as a marker for +4 cells, since a LacZ knock-in allele shows the strongest expression here (Takeda et al., 2011). Indeed, the +4 position is also the most frequent site for lineage-tracing events using a Hopx-CreER transgenic allele. Hopx+ cells may give rise to all intestinal lineages, including Lgr5+ CBCs. It has also been shown that Lgr5+ cells may produce Hopx+ cells at the +4 position. A high level of Hopx expression has been reported in Lgr5+ cells (Barker et al., 2012). These findings further support a model in which transdifferentiation between fastand slow-cycling ISC lineages occurs even under unstressed conditions. Thus, two stem cell populations may populate the crypts of the GIT. In primary CRC, Hopx has been reported to be methylated and dramatically downregulated, suggesting that Hopx expression may be epigenetically repressed in cancers (Yamashita et al., 2013). Indeed, the methylation status of the Hopx gene has been linked to the differentiation status of CRC. However, it is currently unclear whether Hopx is a marker for CRCSCs.

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