Sox2 Suppresses Gastric Tumorigenesis in Mice
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Author
Sarkar, Abby
Sulahian, Rita
Anselmo, Anthony
Xu, Xinsen
Flattery, Kyle
Desai, Niyati
Sebastian, Carlos
Yram, Mary Anna
Arnold, Katrin
Published Version
https://doi.org/10.1016/j.celrep.2016.07.034Metadata
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Sarkar, Abby, Aaron Huebner, Rita Sulahian, Anthony Anselmo, Xinsen Xu, Kyle Flattery, Niyati Desai et al. "Sox2 Suppresses Gastric Tumorigenesis in Mice." Cell Reports 16, no. 7 (2016): 1929-1941. DOI: 10.1016/j.celrep.2016.07.034Abstract
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.Terms of Use
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https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37369689
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