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Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy [CUTnTag_Ezh2i]

GSE242436 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 9 samples Submitted 2024/07/26 Platform GPL21697
Summary
While cell fate determination and maintenance are important in establishing and preserving tissue identity and function during development, aberrant cell fate transition leads to cancer cell heterogeneity and resistance to treatment. Here, we report an unexpected role for the transcription factor p63 (Trp63/TP63) in the fate choice of squamous versus neuroendocrine lineage in esophageal development and malignancy. Deletion of p63 results in extensive neuroendocrine differentiation in the developing mouse esophagus and esophageal progenitors derived from human embryonic stem cells. In human esophageal neuroendocrine carcinoma (eNEC) cells, p63 is transcriptionally silenced by EZH2-mediated H3K27 trimethylation (H3K27me3). Upregulation of the major p63 isoform ΔNp63α, through either ectopic expression or EZH2 inhibition, promotes squamous transdifferentiation of eNEC cells. Together these findings uncover p63 as a rheostat in coordinating the transition between squamous and neuroendocrine cell fates during esophageal development and tumor progression.
Published in
Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy
Zhang Y, Karagiannis D, Liu H et al. · Science advances 2024 · PMID 39383220 · doi:10.1126/sciadv.adq0479
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Also filed as BioProject PRJNA1013441 and SRA study SRP458765. Searching any of these in the dataset finder brings you back here.

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