The Intestinal Wnt/TCF Signature

Transgenic expression of oncogenic BRAF induces loss of stem cells in the mouse intestine, which is antagonized by β-catenin activity

“…We evaluated gene signatures comprising MAPK or β-catenin target genes, as well as signature genes enriched in stem cells or proliferative committed TA cells of the intestinal epithelium. [29][30][31][32] As expected, we found that a signature of MAPK target genes was strongly induced by BRAF V600K in ISCs when compared with luciferase-expressing control ISCs. However, signatures of β-catenin target genes were not significantly changed.…”

Attenuation of the beta-catenin/TCF4 complex in colorectal cancer cells induces several growth-suppressive microRNAs that target cancer promoting genes

“…The 60 dnTCF4-responsive miRNAs were encoded by 62 miRNA hairpins, and 47% (29 out of 62) of these was localized within a total of 26 host genes that is similar to the background frequency of 45% (315 out of 701) in miRBase v12 (Supplementary Table S2). By annotating miRNA host genes in a previously described microarray data set derived from dnTCF4-induced mRNA changes in the same cell model (Van der Flier et al, 2007), we only found five host genes to show at least twofold change and four of these were in the same direction as their relevantly paired miRNAs, suggesting a synchronized production of both mRNA and miRNA species from a shared promoter (Figure 1b). Overall, however, it appeared as if most dnTCF4-responsive miRNAs were not altered as a consequence of host gene expression, albeit differences in stability and processing kinetics may be responsible for some of the diverging patterns observed.…”

“…Bioinformatic analyses involving identification of miRNA hairpins in proximity of ChIP-chip TCF4 binding sites retrieved from a previous report (Hatzis et al, 2008), and host gene analysis using the previously described dox-dnTCF4 gene expression profiles kindly provided by Van der Flier et al (2007) are described in Supplementary Methods.…”

Modeling colorectal cancer as a 3-dimensional disease in a dish: the case for drug screening using organoids, zebrafish, and fruit flies

“…In 2007 and 2008, a variety of intestinal stem cell (ISC) specific markers were identified [20], leading to the unequivocal identification of two distinct classes of stem cells: a rapidly cycling population of Lgr5-expressing cells located at the crypt base [21] and a quiescent population of Bmi1-expressing cells located at the +4 position relative to the crypt base cells [22] reviewed by Li and Clevers [23] (Fig. 1).…”

“…As a case in point, two of the genes missing from the tumor Lgr5 signature are Lgr5 itself and Axin, both expressed downstream of the Wnt pathway [20]. Since the Wnt pathway is essential for stem cell maintenance, the lack of expression of some Wnt target genes in tumor Lgr5 cells might suggest that they are missing key elements of stemness.…”