| First Author | Dopeso H | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 4 | Pages | 109400 |
| PubMed ID | 38523777 | Mgi Jnum | J:346583 |
| Mgi Id | MGI:7617983 | Doi | 10.1016/j.isci.2024.109400 |
| Citation | Dopeso H, et al. (2024) RhoA downregulation in the murine intestinal epithelium results in chronic Wnt activation and increased tumorigenesis. iScience 27(4):109400 |
| abstractText | Rho GTPases are molecular switches regulating multiple cellular processes. To investigate the role of RhoA in normal intestinal physiology, we used a conditional mouse model overexpressing a dominant negative RhoA mutant (RhoA(T19N)) in the intestinal epithelium. Although RhoA inhibition did not cause an overt phenotype, increased levels of nuclear beta-catenin were observed in the small intestinal epithelium of RhoA(T19N) mice, and the overexpression of multiple Wnt target genes revealed a chronic activation of Wnt signaling. Elevated Wnt signaling in RhoA(T19N) mice and intestinal organoids did not affect the proliferation of intestinal epithelial cells but significantly interfered with their differentiation. Importantly, 17-month-old RhoA(T19N) mice showed a significant increase in the number of spontaneous intestinal tumors. Altogether, our results indicate that RhoA regulates the differentiation of intestinal epithelial cells and inhibits tumor initiation, likely through the control of Wnt signaling, a key regulator of proliferation and differentiation in the intestine. |
