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

Publication ,  Journal Article
Huang, JJ; Corona, AL; Dunn, BP; Cai, EM; Prakken, JN; Blobe, GC
Published in: Oncogene
May 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.

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Published In

Oncogene

DOI

EISSN

1476-5594

Publication Date

May 2019

Volume

38

Issue

18

Start / End Page

3402 / 3414

Location

England

Related Subject Headings

  • Signal Transduction
  • Receptors, Transforming Growth Factor beta
  • Proteoglycans
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice
  • Lung Neoplasms
  • Humans
  • HEK293 Cells
  • Gene Expression Regulation, Neoplastic
 

Citation

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Chicago
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Huang, J. J., Corona, A. L., Dunn, B. P., Cai, E. M., Prakken, J. N., & Blobe, G. C. (2019). Increased type III TGF-β receptor shedding decreases tumorigenesis through induction of epithelial-to-mesenchymal transition. Oncogene, 38(18), 3402–3414. https://doi.org/10.1038/s41388-018-0672-7
Huang, Jennifer J., Armando L. Corona, Brian P. Dunn, Elise M. Cai, Jesse N. Prakken, and Gerard C. Blobe. “Increased type III TGF-β receptor shedding decreases tumorigenesis through induction of epithelial-to-mesenchymal transition.Oncogene 38, no. 18 (May 2019): 3402–14. https://doi.org/10.1038/s41388-018-0672-7.
Huang JJ, Corona AL, Dunn BP, Cai EM, Prakken JN, Blobe GC. Increased type III TGF-β receptor shedding decreases tumorigenesis through induction of epithelial-to-mesenchymal transition. Oncogene. 2019 May;38(18):3402–14.
Huang, Jennifer J., et al. “Increased type III TGF-β receptor shedding decreases tumorigenesis through induction of epithelial-to-mesenchymal transition.Oncogene, vol. 38, no. 18, May 2019, pp. 3402–14. Pubmed, doi:10.1038/s41388-018-0672-7.
Huang JJ, Corona AL, Dunn BP, Cai EM, Prakken JN, Blobe GC. Increased type III TGF-β receptor shedding decreases tumorigenesis through induction of epithelial-to-mesenchymal transition. Oncogene. 2019 May;38(18):3402–3414.

Published In

Oncogene

DOI

EISSN

1476-5594

Publication Date

May 2019

Volume

38

Issue

18

Start / End Page

3402 / 3414

Location

England

Related Subject Headings

  • Signal Transduction
  • Receptors, Transforming Growth Factor beta
  • Proteoglycans
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice
  • Lung Neoplasms
  • Humans
  • HEK293 Cells
  • Gene Expression Regulation, Neoplastic