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 ErbB family consists of four receptor tyrosine kinases (EGFR and Her2 – 4). Maintenance of epithelial homeostasis in the intestinal epithelium is dependent on ErbB signalling, since the ErbB family is expressed in the stem cell niche (Sato et al., 2011). Lrig1 is a transmembrane negative-feedback regulator of ErbB receptor signalling and is increasingly expressed in ISCs. Lrig1 is expressed as frequently as Lgr5, although with limited overlap in the colon (Figure 9.1). Lrig1 expression is considered to mark a quiescent ISC during normal tissue homeostasis in the GIT, but the number of Lrig1+ cells can be expanded following irradiation.

During normal homeostasis, 20% of the Lrig1+ cells are LRCs and 25% express Ki67, whereas after irradiation nonproliferating cells enter the cell cycle. Deletion of the tumour suppressor Apc in Lrig1+ cells leads to the formation of adenomas. Lrig1 may also function as a tumour suppressor, since loss of Lrig1 generates adenomas in the duodenum (Powell et al., 2012). It is unclear to what extent Lgr5 and Lrig1 describe truly distinct cell lineages. Both Lrig1+ and Lgr5+ cells isolated from the colon express CD133, mTERT and Bmi1, and it has been suggested that Lrig1 does not selectively mark a quiescent ISC in the intestine (Barker et al., 2012; Wong et al., 2012). Moreover, a high level of Lrig1-expression is frequently observed in Lgr5+ cells (Munoz et al., 2012; Wong et al., 2012). Thus, it is unclear whether Lrig1 marks quiescent ISCs that are distinct from Lgr5+ cells or if it is a general regulator of the stem cell niche.

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