Active elimination of intestinal cells drives oncogenic growth in organoids

Ana Krotenberg Garcia, Arianna Fumagalli, Huy Quang Le, Rene Jackstadt, Tamsin Rosemary Margaret Lannagan, Owen James Sansom, Jacco van Rheenen, Saskia Jacoba Elisabeth Suijkerbuijk

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

6 Citaten (Scopus)

Samenvatting

Competitive cell interactions play a crucial role in quality control during development and homeostasis. Here, we show that cancer cells use such interactions to actively eliminate wild-type intestine cells in enteroid monolayers and organoids. This apoptosis-dependent process boosts proliferation of intestinal cancer cells. The remaining wild-type population activates markers of primitive epithelia and transits to a fetal-like state. Prevention of this cell-state transition avoids elimination of wild-type cells and, importantly, limits the proliferation of cancer cells. Jun N-terminal kinase (JNK) signaling is activated in competing cells and is required for cell-state change and elimination of wild-type cells. Thus, cell competition drives growth of cancer cells by active out-competition of wild-type cells through forced cell death and cell-state change in a JNK-dependent manner.

Originele taal-2Engels
Artikelnummer109307
TijdschriftCell Reports
Volume36
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 6 jul. 2021
Extern gepubliceerdJa

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