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Review
. 2015 Jun 30;113(1):1-5.
doi: 10.1038/bjc.2015.214. Epub 2015 Jun 25.

Stem vs non-stem cell origin of colorectal cancer

D J Huels  1 , O J Sansom  1
Affiliations
Review

Stem vs non-stem cell origin of colorectal cancer

D J Huels et al. Br J Cancer. .

Abstract

Colorectal cancer (CRC) is one of the most common cancers in the western world and is characterised by deregulation of the Wnt signalling pathway. Mutation of the adenomatous polyposis coli (APC) tumour suppressor gene, which encodes a protein that negatively regulates this pathway, occurs in almost 80% of CRC cases. The progression of this cancer from an early adenoma to carcinoma is accompanied by a well-characterised set of mutations including KRAS, SMAD4 and TP53. Using elegant genetic models the current paradigm is that the intestinal stem cell is the origin of CRC. However, human histology and recent studies, showing marked plasticity within the intestinal epithelium, may point to other cells of origin. Here we will review these latest studies and place these in context to provide an up-to-date view of the cell of origin of CRC.

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Figures

Figure 1
Figure 1
Methods to induce adenoma formation in stem cells and differentiated cells. (A) Overview of a crypt in the small intestine. The crypt base columnar (CBC) cells are located at the bottom of the crypt in between the Paneth cells. In addition to the expression of several stem cell markers, the functionality of the intestinal stem cell (ISC) is determined by its location, with the ‘centre' ISC having the highest ISC functionality. (B) The expression of specific stem cell markers has been used to induce cre-driven recombination in ISCs, leading to adenoma formation, either by loss of Apc or Bcatex3 mutation. Oral administration of low-dose β-naphthoflavone has been used to induce AhCre-dependent Apc loss in cells above the crypt base, resulting in formation of microadenomas. Recombination in differentiated villus cells only resulted in adenomas when Apc loss or Bcatex3 mutation was combined with Kras mutation or NFKB activation (villus purification in VilCreER mice or Xbp1sCreER).
See this image and copyright information in PMC

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