Secreted stromal protein ISLR promotes intestinal regeneration by suppressing epithelial Hippo signaling

ABSTRACT: The Hippo-YAP signaling pathway plays an essential role in epithelial cells during intestinal regeneration and tumorigenesis. However, the molecular mechanism linking stromal signals to YAP-mediated intestinal regeneration and tumorigenesis is poorly defined. Here we report a stroma-epithelia ISLR-YAP signaling axis essential for stromal cells to modulate epithelial cell growth during intestinal regeneration and tumorigenesis. Specifically, upon inflammation and in cancer, an oncogenic transcription factor ETS1 in stromal cells induces expression of a secreted protein ISLR that can inhibit Hippo signaling and activate YAP in epithelial cells. Deletion of Islr in stromal cells in mice markedly impaired intestinal regeneration, and suppressed tumorigenesis in the colon. Moreover, the express

SUBMITTER: Dr. Jiuzhi Xu 

PROVIDER: S-SCDT-EMBOJ-2019-103255 | biostudies-other |

REPOSITORIES: biostudies-other