Canonical TGFβ signaling induces collective invasion in colorectal carcinogenesis through a Snail1- and Zeb1-independent partial EMT.

ABSTRACT: Local invasion is the initial step towards metastasis, the main cause of cancer mortality. In human colorectal cancer (CRC), malignant cells predominantly invade as cohesive collectives and may undergo partial epithelial-mesenchymal transition (pEMT) at the invasive front. How this particular mode of stromal infiltration is generated is unknown. Here we investigated the impact of oncogenic transformation and the microenvironment on tumor cell invasion using genetically engineered organoids as CRC models. We found that inactivation of the Apc tumor suppressor combined with expression of oncogenic Kras^G12D and dominant-negative Trp53^R172H did not cell-autonomously induce invasion in vitro. However, oncogenic transformation primed organoids for activation of a collective

SUBMITTER: Flum M 

PROVIDER: S-EPMC8897192 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature