PT  - JOURNAL ARTICLE
AU  - Chen, Qing
AU  - Suzuki, Kohei
AU  - Sifuentes-Dominguez, Luis
AU  - Miyata, Naoteru
AU  - Song, Jie
AU  - Lopez, Adam
AU  - Starokadomskyy, Petro
AU  - Gopal, Purva
AU  - Dozmorov, Igor
AU  - Tan, Shuai
AU  - Ge, Bujun
AU  - Burstein, Ezra
TI  - Paneth cell–derived growth factors support tumorigenesis in the small intestine
AID  - 10.26508/lsa.202000934
DP  - 2021 Mar 01
TA  - Life Science Alliance
PG  - e202000934
VI  - 4
IP  - 3
4099  - https://www.life-science-alliance.org/content/4/3/e202000934.short
4100  - https://www.life-science-alliance.org/content/4/3/e202000934.full
SO  - Life Sci. Alliance2021 Mar 01; 4
AB  - Paneth cells (PCs) are small intestinal epithelial cells that secrete antimicrobial peptides and growth factors, such as Wnt ligands. Intriguingly, the context in which PC-derived Wnt secretion is relevant in vivo remains unknown as intestinal epithelial ablation of Wnt does not affect homeostatic proliferation or restitution after irradiation injury. Considering the importance of growth factors in tumor development, we explored here the role of PCs in intestinal carcinogenesis using a genetic model of PC depletion through conditional expression of diphtheria toxin-α subunit. PC depletion in ApcMin mice impaired adenoma development in the small intestine and led to decreased Wnt3 expression in small bowel adenomas. To determine if PC-derived Wnt3 was required for adenoma development, we examined tumor formation after PC-specific ablation of Wnt3. We found that this was sufficient to decrease small intestinal adenoma formation; moreover, organoids derived from these tumors displayed slower growth capacity. Overall, we report that PC-derived Wnt3 is required to sustain early tumorigenesis in the small bowel and identify a clear role for PC-derived Wnt production in intestinal pathology.