SNAI1 expression is up-regulated in colorectal cancer and correlates with intestinal stem cell markers

R Akhtar1, K Horvay1, T Jarde1,2, L Kass1, P Carne3, K Oliva3, GR Hime4, PJ McMurrick3 and HE Abud1

  1. Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia
  2. Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Australia
  3. Department of Surgery, Cabrini Monash University, Malvern, Victoria, Australia
  4. Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia

SNAIL family of transcriptional regulators (SNAI1, SNAI2 and SNAI3) are well known for their role in mediating epithelial-mesenchymal transitions (EMTs), which is fundamental for the acquisition of tumour invasiveness (Hay 1995). Members of the Snail family have been shown to be upregulated in several human cancers and are frequently associated with poor prognosis (Peinado et al. 2007). However, not much is known about their role in regulating epithelial cancer stem cells. Our previous study suggests that up-regulation of Snai1 in the normal mouse small intestinal epithelium results in an increase in intestinal stem cell (ISC) number and epithelial cell proliferation (Horvay et al 2015). The aim of this project is to investigate the role of the SNAIL proteins in colorectal cancer and whether these molecules regulate cancer stem cells. Expression levels of SNAIL family members and ISC markers were analysed in tumour and matched normal tissues collected from 69 colorectal cancer patients by Droplet Digital PCR (ddPCR) and were compared with clinical data. Results from this study suggest that SNAI1 is upregulated in colorectal cancer and expression of SNAIL family members correlates with expression of intestinal stem cell markers in these patients. Moreover, expression of SNAI1 has been found to correlate with tumour stage in this patient cohort. We are also examining the functional role of Snai1 in mouse models of intestinal polyp formation.
References: Hay ED (1995). An overview of epithelio-mesenchymal transformation. Acta Anat 154: 8–20. Peinado H, Olmeda D, Cano A (2007). Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 7: 415–28. Horvay K, Thierry J, Casagranda F, Perreau VM, Haigh K, Nefzger CM et al. (2015) Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium. EMBO J 34(10): 1319–35.