EPHA2-dependent outcompetition of KRASG12D mutant cells by wild-type neighbors in the adult pancreas.

ABSTRACT: As we age, our tissues are repeatedly challenged by mutational insult, yet cancer occurrence is a relatively rare event. Cells carrying cancer-causing genetic mutations compete with normal neighbors for space and survival in tissues. However, the mechanisms underlying mutant-normal competition in adult tissues and the relevance of this process to cancer remain incompletely understood. Here, we investigate how the adult pancreas maintains tissue health in vivo following sporadic expression of oncogenic Kras (KrasG12D), the key driver mutation in human pancreatic cancer. We find that when present in tissues in low numbers, KrasG12D mutant cells are outcompeted and cleared from exocrine and endocrine compartments in vivo. Using quantitative 3D tissue imaging, we show that before being cleared

SUBMITTER: Hill W 

PROVIDER: S-EPMC8231095 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature