| First Author | Liu H | Year | 2017 |
| Journal | Dev Cell | Volume | 41 |
| Issue | 4 | Pages | 392-407.e6 |
| PubMed ID | 28535374 | Mgi Jnum | J:255302 |
| Mgi Id | MGI:6114582 | Doi | 10.1016/j.devcel.2017.04.024 |
| Citation | Liu H, et al. (2017) Discovery of Stromal Regulatory Networks that Suppress Ras-Sensitized Epithelial Cell Proliferation. Dev Cell 41(4):392-407.e6 |
| abstractText | Mesodermal cells signal to neighboring epithelial cells to modulate their proliferation in both normal and disease states. We adapted a Caenorhabditis elegans organogenesis model to enable a genome-wide mesodermal-specific RNAi screen and discovered 39 factors in mesodermal cells that suppress the proliferation of adjacent Ras pathway-sensitized epithelial cells. These candidates encode components of protein complexes and signaling pathways that converge on the control of chromatin dynamics, cytoplasmic polyadenylation, and translation. Stromal fibroblast-specific deletion of mouse orthologs of several candidates resulted in the hyper-proliferation of mammary gland epithelium. Furthermore, a 33-gene signature of human orthologs was selectively enriched in the tumor stroma of breast cancer patients, and depletion of these factors from normal human breast fibroblasts increased proliferation of co-cultured breast cancer cells. This cross-species approach identified unanticipated regulatory networks in mesodermal cells with growth-suppressive function, exposing the conserved and selective nature of mesodermal-epithelial communication in development and cancer. |
