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Epithelial aPKC deficiency leads to stem cell loss preceding metaplasia in colorectal cancer initiation [RNA-Seq]

GSE236649 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2024/07/05 Platform GPL19057
Summary
The early mechanisms of spontaneous tumor initiation that precede the accumulation of cancer mutations are largely unknown. We show that reduced aPKC levels correlate with stem cell loss and the induction of revival and metaplastic programs in serrated- and conventional-initiated pre-neoplastic lesions, which is perpetuated in colorectal cancers (CRC). Acute inactivation of PKCl/i in vivo and in organoids is sufficient to stimulate JNK in non-transformed intestinal epithelial cells (IECs), which promotes cell death and the rapid loss of the intestinal stem cells (ISC), including LGR5+ cells. This is followed by the accumulation of revival stem cells (RSC) at the bottom of the crypt and fetal metaplastic cells (FMC) at the top, creating two spatiotemporally distinct cell populations that depend on JNK-induced AP-1 and YAP. These cell lineage changes are maintained during cancer initiation and progression and determine the aggressive phenotype of human CRC irrespective of their serrated or conventional origin
Published in
Enhanced SREBP2-driven cholesterol biosynthesis by PKCλ/ι deficiency in intestinal epithelial cells promotes aggressive serrated tumorigenesis
Muta Y, Linares JF, Martinez-Ordoñez A et al. · Nature communications 2023 · PMID 38092754 · doi:10.1038/s41467-023-43690-5
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Also filed as BioProject PRJNA991964 and SRA study SRP447644. Searching any of these in the dataset finder brings you back here.

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