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Article Dans Une Revue eLife Année : 2022

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

Wenjie Sun
Zeinab Homayed
Julie Pannequin

Résumé

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.
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Dates et versions

hal-03672160 , version 1 (16-11-2022)

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Guillaume Jacquemin, Annabelle Wurmser, Mathilde Huyghe, Wenjie Sun, Zeinab Homayed, et al.. Paracrine signalling between intestinal epithelial and tumour cells induces a regenerative programme. eLife, 2022, 11, pp.e76541. ⟨10.7554/eLife.76541⟩. ⟨hal-03672160⟩
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