Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

<jats:title>Abstract</jats:title><jats:p>Genotoxic colibactin-producing <jats:italic>pks</jats:italic>+ <jats:italic>Escherichia coli</jats:italic> induce DNA double-strand breaks, mutations, and promote tumor development in mouse models of colorectal cancer (CRC). Colibactin’s distinct mutational signature is reflected in human CRC, suggesting a causal link. Here, we investigate its transformation potential using organoids from primary murine colon epithelial cells. Organoids recovered from short-term infection with <jats:italic>pks</jats:italic>+ <jats:italic>E. coli</jats:italic> show characteristics of CRC cells, e.g., enhanced proliferation, Wnt-independence, and impaired differentiation. Sequence analysis of Wnt-independent organoids reveals an enhanced mutational burden, including chromosomal aberrations typical of genomic instability. Although we do not find classic Wnt-signaling mutations, we identify several mutations in genes related to p53-signaling, including <jats:italic>miR-34a</jats:italic>. Knockout of <jats:italic>Trp53</jats:italic> or <jats:italic>miR-34</jats:italic> in organoids results in Wnt-independence, corroborating a functional interplay between the p53 and Wnt pathways. We propose larger chromosomal alterations and aneuploidy as the basis of transformation in these organoids, consistent with the early appearance of chromosomal instability in CRC.</jats:p>

Original publication




Journal article


Nature Communications


Springer Science and Business Media LLC

Publication Date