WEE1 inhibition alleviates resistance to immune attack of tumor cells undergoing epithelial-mesenchymal transition.

ABSTRACT: Aberrant expression of the T-box transcription factor brachyury in human carcinomas drives the phenomenon of epithelial-mesenchymal transition (EMT), a phenotypic modulation that facilitates tumor dissemination and resistance to conventional therapies, including chemotherapy and radiotherapy. By generating isogenic cancer cell lines with various levels of brachyury expression, we demonstrate that high levels of brachyury also significantly reduce the susceptibility of cancer cells to lysis by both antigen-specific T cells and natural killer cells. Our results indicated that resistance of brachyury-high tumor cells to immune-mediated attack was due to inefficient caspase-dependent apoptosis, manifested as inefficient nuclear lamin degradation in the presence of activated effector caspases.

SUBMITTER: Hamilton DH 

PROVIDER: S-EPMC4011139 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature