Paneth cell–derived growth factors support tumorigenesis in the small intestine

@article{Chen2020PanethCG,
  title={Paneth cell–derived growth factors support tumorigenesis in the small intestine},
  author={Qing Chen and Kohei Suzuki and Luis F Sifuentes-Dominguez and Naoteru Miyata and Jie Song and Adam M. Lopez and Petro Starokadomskyy and Purva Gopal and Igor Dozmorov and Shuai Tan and BuJun Ge and Ezra Burstein},
  journal={Life Science Alliance},
  year={2020},
  volume={4}
}
Paneth cells, known for their production of antimicrobial peptides and growth factors in the gut epithelium, are found to play a key role in intestinal tumor formation through secretion of Wnt3. 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… 
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References

SHOWING 1-10 OF 46 REFERENCES
Examining the Role of Paneth Cells in the Small Intestine by Lineage Ablation in Transgenic Mice*
TLDR
The findings suggest that stemness in the crypt is not defined by instructive interactions involving the Paneth cell, and that this lineage does not function to maintain the asymmetric crypt-villus distribution of components of the diffuse gut-associated lymphoid tissue.
Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts
TLDR
It is concluded that epithelial Wnts are dispensable and that stromal production of WNTs can fully support normal murine intestinal homeostasis.
Functional intestinal stem cells after Paneth cell ablation induced by the loss of transcription factor Math1 (Atoh1)
TLDR
It is found that complete loss of Paneth cells attributable to Math1 deficiency did not perturb the crypt architecture and allowed the maintenance and proliferation of CBCs, and CBC stem cells deficient in adenomatous polyposis coli and Math1 were able to promote intestinal tumorigenesis.
Paneth cell marker expression in intestinal villi and colon crypts characterizes dietary induced risk for mouse sporadic intestinal cancer
TLDR
In a mouse model of dietary-induced sporadic small and large intestinal cancer in WT mice, common intestinal cancer driven by diet involves mechanisms of tumor development distinct from those mechanisms that cause tumors induced by the rare inheritance of a mutant adenomatous polyposis coli (Apc) allele.
Paneth cells: maestros of the small intestinal crypts.
TLDR
Investigation over the past several decades determined that Paneth cells synthesize and secrete substantial quantities of antimicrobial peptides and proteins, which are key mediators of host-microbe interactions, including homeostatic balance with colonizing microbiota and innate immune protection from enteric pathogens.
Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
TLDR
It is concluded that Lgr5 stem cells compete for essential niche signals provided by a specialized daughter cell, the Paneth cell, in colon crypts, and co-culturing of sorted stem cells with Paneth cells markedly improves organoid formation.
Subepithelial telocytes are an important source of Wnts that supports intestinal crypts
TLDR
Subepithelial telocytes are identified as a source of Wnt signals that enable proliferation and differentiation of intestinal stem cells, an essential function for maintenance of the intestinal epithelium.
Extrinsic control of Wnt signaling in the intestine.
  • S. Koch
  • Biology
    Differentiation; research in biological diversity
  • 2017
Wnt signaling in adult intestinal stem cells and cancer.
Intact function of Lgr5 receptor-expressing intestinal stem cells in the absence of Paneth cells
TLDR
In the sustained absence of Paneth cells, Lgr5+ CBCs occupied the full crypt base, proliferated briskly, and generated differentiated progeny over many months, and Gene expression in fluorescence-sorted Lgr4-nonexpressing CBCs reflected intact Wnt signaling despite the loss ofPaneth cells.
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