Infection with genotoxin-producing Salmonella enterica synergises with loss of the tumour suppressor APC in promoting genomic instability via the PI3K pathway in colonic epithelial cells.
Examples have included phosphatase and tensin homolog deleted on chromosome ten (PTEN), a tumor suppressor that inhibits PI3K/pAkt signaling, Rb1, the protein involved in retinoblastoma development, and adenomatous polyposis coli (APC), a tumor suppressor that inhibits β-Catenin transcriptional signaling and its translocation to the nucleus.
This response was also confirmed with <sup>18</sup>F-FDG microPET/CT imaging.<b>Implications:</b> Spheroid models and transgenic mice suggest that dual PI3K/mTOR inhibition is a potential treatment strategy for <i>APC</i> and <i>PIK3CA</i>-mutant colorectal cancers.
PTEN inactivation by mutation or allelic loss also occurs in CRCs. miR‑135b was reported to be upregulated in CRCs and its overexpression was due to APC/β‑catenin and PTEN/PI3K pathway deregulation.
Here, we demonstrate that expression of a dominant active PI3K synergizes with loss of APC activity resulting in a dramatic change in tumor multiplicity, size, morphology and invasiveness.