| Literature DB >> 27498859 |
Abby Sarkar1, Aaron J Huebner1, Rita Sulahian2, Anthony Anselmo3, Xinsen Xu4, Kyle Flattery1, Niyati Desai5, Carlos Sebastian6, Mary Anna Yram1, Katrin Arnold1, Miguel Rivera5, Raul Mostoslavsky6, Roderick Bronson7, Adam J Bass4, Ruslan Sadreyev3, Ramesh A Shivdasani2, Konrad Hochedlinger8.
Abstract
Sox2 expression marks gastric stem and progenitor cells, raising important questions regarding the genes regulated by Sox2 and the role of Sox2 itself during stomach homeostasis and disease. By using ChIP-seq analysis, we have found that the majority of Sox2 targets in gastric epithelial cells are tissue specific and related to functions such as endoderm development, Wnt signaling, and gastric cancer. Unexpectedly, we found that Sox2 itself is dispensable for gastric stem cell and epithelial self-renewal, yet Sox2(+) cells are highly susceptible to tumorigenesis in an Apc/Wnt-driven mouse model. Moreover, Sox2 loss enhances, rather than impairs, tumor formation in Apc-deficient gastric cells in vivo and in vitro by inducing Tcf/Lef-dependent transcription and upregulating intestinal metaplasia-associated genes, providing a mechanistic basis for the observed phenotype. Together, these data identify Sox2 as a context-dependent tumor suppressor protein that is dispensable for normal tissue regeneration but restrains stomach adenoma formation through modulation of Wnt-responsive and intestinal genes.Entities:
Mesh：
Substances：
Year: 2016 PMID： 27498859 DOI： 10.1016/j.celrep.2016.07.034
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423