RESUMO
The type III TGF-ß receptor (TßRIII) is a TGF-ß co-receptor that presents ligand to the type II TGF-ß receptor to initiate signaling. TßRIII also undergoes ectodomain shedding to release a soluble form (sTßRIII) that can bind ligand, sequestering it away from cell surface receptors. We have previously identified a TßRIII extracellular mutant that has enhanced ectodomain shedding ("super shedding (SS)"-TßRIII-SS). Here, we utilize TßRIII-SS to study the balance of cell surface and soluble TßRIII in the context of lung cancer. We demonstrate that expressing TßRIII-SS in lung cancer cell models induces epithelial-to-mesenchymal transition (EMT) and that these TßRIII-SS (EMT) cells are less migratory, invasive and adhesive and more resistant to gemcitabine. Moreover, TßRIII-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 TßRIII may regulate a dichotomous role for TßRIII during cancer progression.