Paracrine signalling between intestinal epithelial and tumour cells induces a regenerative programme

Tumours are complex ecosystems composed of different types of cells that communicate and influence each other. While the critical role of stromal cells in affecting tumour growth is well established, the impact of mutant cancer cells on healthy surrounding tissues remains poorly defined. Here, using mouse intestinal organoids, we uncover a paracrine mechanism by which intestinal cancer cells reactivate foetal and regenerative YAP-associated transcriptional programmes in neighbouring wildtype epithelial cells, rendering them adapted to thrive in the tumour context. We identify the glycoprotein thrombospondin-1 (THBS1) as the essential factor that mediates non-cell-autonomous morphological and transcriptional responses. Importantly, Thbs1 is associated with bad prognosis in several human cancers. This study reveals the THBS1-YAP axis as the mechanistic link mediating paracrine interactions between epithelial cells in intestinal tumours.


Sample-size estimation
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Replicates
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This information is indicated in the figure legends and/or in the Methods section. No technical replicate was represented or used for statistical analysis, only biological replicates were considered. No data was excluded from this study. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD02000247. The RNA sequencing data have been deposited in the Gene Expression Omnibus (GEO) repository under accession code GSE153160: Whole-genome transcriptomic analysis of intestinal organoids and tumoroids.

Statistical reporting
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