Figure 8: Hmga1 in normal intestinal homeostasis and reprogramming to neoplasia.

(a) There is a significant positive correlation (r=0.51; P=0.008) between HMGA1 and SOX9 in control, non-malignant large intestinal epithelium by Spearman’s correlation (n=26). There is also a highly significant upregulation of both HMGA1 and SOX9 in colorectal cancer (n=293, P<0.000001). Boxplots, scatterplots and Spearman rank-based correlations were calculated using R statistical software. (b) Model depicting normal ISC function and tissue homeostasis in the large intestine under conditions of tightly regulated Hmga1 expression and Wnt signalling (left). Intestinal epithelium homeostasis is disrupted (right) in the setting of aberrant Hmga1 expression, leading to expansion in the ISC compartment, excessive Wnt signalling, and abnormal proliferation, culminating in epithelial reprogramming to neoplastic, transformed cells. (c) Model depicting normal ISC function and tissue homeostasis in the small intestine under conditions of tightly regulated Hmga1 expression, Paneth cell differentiation and Wnt signalling (left). Expansion in the ISCs and Paneth cell niche occurs when homeostasis is disrupted (right) in the setting of aberrant Hmga1 expression. This contributes to amplified Wnt signalling, abnormal proliferation, epithelial reprogramming and neoplastic transformation.