RT Journal Article
SR Electronic
T1 Paneth cell–derived growth factors support tumorigenesis in the small intestine
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000934
DO 10.26508/lsa.202000934
VO 4
IS 3
A1 Qing Chen
A1 Kohei Suzuki
A1 Luis Sifuentes-Dominguez
A1 Naoteru Miyata
A1 Jie Song
A1 Adam Lopez
A1 Petro Starokadomskyy
A1 Purva Gopal
A1 Igor Dozmorov
A1 Shuai Tan
A1 Bujun Ge
A1 Ezra Burstein
YR 2021
UL https://www.life-science-alliance.org/content/4/3/e202000934.abstract
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.