The role of Sox4 in normal intestines and colorectal cancer (2014)

Undergraduates: Danny Trotier, Adam Gracz

Faculty Advisor: Scott Magness
Department: Biology

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Sry-box containing (Sox) factors are versatile regulators of cell fate and proliferation in a wide range of tissues, and recent research has demonstrated that Sox4 is expressed in the stem cell zone of the small intestinal epithelium. To examine the mechanistic role of Sox4 in the epithelium, we utilize a conditional knockout mouse model to demonstrate that intestinal epithelial-specific loss of Sox4 leads to an increase in markers of proliferation and downstream targets of the Wnt pathway. Sox4 knockout animals exhibit intestinal crypt hyperplasia in vivo, which is consistent with constitutively active Wnt signaling. We also observed secretory lineage allocation defects in the intestines of Sox4 knockout animals, which exhibit an increase in Paneth cell numbers and a decrease in enteroendocrine cells relative to wild type controls. Together, these results suggest that Sox4 contributes to maintaining the balance of proliferation and differentiation in the intestinal epithelium, and plays a role in the regulation of intestinal stem cells. In the tumor context, Sox4 may be playing an alternate role by promoting Epithelial-Mesenchymal-Transition in a mouse model of colorectal cancer. Preliminary data suggests Sox4 is aberrantly activated in tumors and is promoting an EMT program that may facilitate tumor progression and metastasis.