Nucs-Associated Mutation Avoidance in Mycobacteria and Its Association with Antibiotic Resistance

Genetic and epigenetic changes provide survival advantages for stem or progenitor cells resulting in the deregulation of cellular differentiation. In colorectal cancer (CRC), this is reflected by the low frequencies of goblet cells. Understanding the mechanisms involved in goblet cell differentiation is, therefore, important for advances in the prevention and treatment of CRC. Our laboratory has a large collection of CRC cell lines, well characterised in terms of gene expression and mutations. We analysed the presence of goblet cells in our panel of cell lines using the genes Mucin 2 (MUC2) and Trefoil factor 3 (TFF3) as goblet cell markers. We found that most of the cell lines are unable to produce goblet cells and that the number of MUC2 and TFF3 positive cells among the goblet cell positive cell lines was quite variable. MUC2-negative, and TFF3-positive cell lines appear to reflect a novel interesting subset of CRC cell lines.

We also investigated the effect of transcription factors on goblet cell differentiation. Downregulation of Atonal homologue 1 (ATOH1) had a dramatic effect on goblet cell production in several CRC cell lines, while knocking down of SAM pointed domain ETS transcription factor (SPDEF), Caudal type homeobox 1 (CDX1), and 2 (CDX2) had a modest effect. Exogenous expression showed that, individually, none of these factors are sufficient on their own to trigger the differentiation of goblet cells. An improved understanding of cell differentiation will contribute to the treatment of colorectal carcinoma.