Therapeutic interference with mTorc1 restricts inflammation-associated and Stat3-dependent gastro-intestinal tumourigenesis in mice

ABSTRACT: Gp130 receptor engagement on neoplastic cells provides a link by which an inflammatory microenvironment facilitates tumour promotion. Although hyperactivation of the gp130-dependent Stat3 signalling node is commonly observed in solid tumours, Stat3 remains a challenging therapeutic target. To mimic excessive Stat3 signalling, we molecularly validate the gp130FF mouse as a preclinical model for inflammation-associated intestinal-type gastric cancer (IGC), with aberrant mammalian target of rapamycin (mTOR) pathway activity as shared feature. Accordingly, administration of the mTorc1 inhibitor RAD001 reversibly reduced IGC burden in gp130FF mice and suppressed colitis-associated cancer in wild-type mice. Since the therapeutic effect of RAD001 occurs independently of Stat3 hyperactivation, whi

ORGANISM(S): Mus musculus

SUBMITTER: Zhengdeng Lei 

PROVIDER: E-GEOD-35808 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress