Increased type III TGF-? receptor shedding decreases tumorigenesis through induction of epithelial-to-mesenchymal transition.

ABSTRACT: The type III TGF-? receptor (T?RIII) is a TGF-? co-receptor that presents ligand to the type II TGF-? receptor to initiate signaling. T?RIII also undergoes ectodomain shedding to release a soluble form (sT?RIII) that can bind ligand, sequestering it away from cell surface receptors. We have previously identified a T?RIII extracellular mutant that has enhanced ectodomain shedding ("super shedding (SS)"-T?RIII-SS). Here, we utilize T?RIII-SS to study the balance of cell surface and soluble T?RIII in the context of lung cancer. We demonstrate that expressing T?RIII-SS in lung cancer cell models induces epithelial-to-mesenchymal transition (EMT) and that these T?RIII-SS (EMT) cells are less migratory, invasive and adhesive and more resistant to gemcitabine. Moreover, T?RIII-SS (EMT) cells exhibit decreased tumorigenicity but increased growth rate in vitro and in vivo. These studies suggest that the balance of cell surface and soluble T?RIII may regulate a dichotomous role for T?RIII during cancer progression.

SUBMITTER: Huang JJ 

PROVIDER: S-EPMC6586422 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature