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

Jennifer J Huang | Armando L Corona | Brian P Dunn | Elise M Cai | Jesse N Prakken | Gerard C Blobe
Oncogene | 2019

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

Pubmed ID: 30643193

Associated grants

  • Agency: U.S. Department of Health & Human Services | National Institutes of Health (NIH), International
    Id: F30CA196162
  • Agency: NCI NIH HHS, United States
    Id: R01 CA135006
  • Agency: NCI NIH HHS, United States
    Id: F30 CA196162
  • Agency: NCI NIH HHS, United States
    Id: P30 CA014236
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007171
  • Agency: U.S. Department of Health & Human Services | National Institutes of Health (NIH), International
    Id: R01CA135006

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