A RAC-GEF network critical for early intestinal tumourigenesis.

ABSTRACT: RAC1 activity is critical for intestinal homeostasis, and is required for hyperproliferation driven by loss of the tumour suppressor gene Apc in the murine intestine. To avoid the impact of direct targeting upon homeostasis, we reasoned that indirect targeting of RAC1 via RAC-GEFs might be effective. Transcriptional profiling of Apc deficient intestinal tissue identified Vav3 and Tiam1 as key targets. Deletion of these indicated that while TIAM1 deficiency could suppress Apc-driven hyperproliferation, it had no impact upon tumourigenesis, while VAV3 deficiency had no effect. Intriguingly, deletion of either gene resulted in upregulation of Vav2, with subsequent targeting of all three (Vav2^-/- Vav3^-/- Tiam1^-/-), profoundly suppressing hyperproliferation, tum

SUBMITTER: Pickering KA 

PROVIDER: S-EPMC7782582 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature