Inhibition of Twist1-mediated invasion by Chk2 promotes premature senescence in p53-defective cancer cells.

ABSTRACT: Twist1, a basic helix-loop-helix transcription factor is implicated as a key mediator of epithelial-mesenchymal transition (EMT) and metastatic dissemination in p53-deficient cancer cells. On the other hand, checkpoint kinase 2 (Chk2), a major cell cycle regulatory protein provides a barrier to tumorigenesis due to DNA damage response by preserving genomic stability of the cells. Here we demonstrate that Chk2 induction proficiently abrogates invasion, cell scattering and invadopodia formation ability of p53-mutated invasive cells by suppressing Twist1, indicating Chk2 confers vital role in metastasis prevention. In addition, ectopic Chk2, as well as its (Chk2) induction by natural podophyllotoxin analog, 4'-demethyl-deoxypodophyllotoxin glucoside (4DPG), strongly restrain Twist1 activity a

SUBMITTER: Nayak D 

PROVIDER: S-EPMC5520175 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature