Active elimination of intestinal cells drives oncogenic growth in organoids.
Cell Rep
; 36(1): 109307, 2021 07 06.
Article
in En
| MEDLINE
| ID: mdl-34233177
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Organoids
/
Carcinogenesis
/
Intestines
Limits:
Animals
Language:
En
Journal:
Cell Rep
Year:
2021
Document type:
Article
Affiliation country:
Países Bajos