Combinatorial interventions inhibit TGFβ-driven epithelial-to-mesenchymal transition and support hybrid cellular phenotypes.

ABSTRACT: Epithelial-to-mesenchymal transition (EMT) is a developmental process hijacked by cancer cells to leave the primary tumor site, invade surrounding tissue and establish distant metastases. A hallmark of EMT is the loss of E-cadherin expression, and one major signal for the induction of EMT is transforming growth factor beta (TGFβ), which is dysregulated in up to 40% of hepatocellular carcinoma (HCC). We aim to identify network perturbations that suppress TGFβ-driven EMT, with the goal of suppressing invasive properties of cancer cells. We use a systems-level Boolean dynamic model of EMT to systematically screen individual and combination perturbations (inhibition or constitutive activation of up to four nodes). We use a recently developed network control approach to understand the mechanism

SUBMITTER: Steinway SN 

PROVIDER: S-EPMC5516807 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature