Journal Article

The type III TGF-β receptor suppresses breast cancer progression through GIPC-mediated inhibition of TGF-β signaling

Jason D. Lee, Nadine Hempel, Nam Y. Lee and Gerard C. Blobe

in Carcinogenesis

Volume 31, issue 2, pages 175-183
Published in print February 2010 | ISSN: 0143-3334
Published online December 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp271
The type III TGF-β receptor suppresses breast cancer progression through GIPC-mediated inhibition of TGF-β signaling

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Loss of expression of the type III transforming growth factor-β receptor (TβRIII or betaglycan), a transforming growth factor-β (TGF-β) superfamily co-receptor, is common in human breast cancers. TβRIII suppresses cancer progression in vivo by reducing cancer cell migration and invasion by largely unknown mechanisms. Here, we demonstrate that the cytoplasmic domain of TβRIII is essential for TβRIII-mediated downregulation of migration and invasion in vitro and TβRIII-mediated inhibition of breast cancer progression in vivo. Functionally, the cytoplasmic domain of TβRIII is required to attenuate TGF-β signaling, whereas TβRIII-mediated attenuation of TGF-β signaling is required for TβRIII-mediated inhibition of migration and invasion. Mechanistically, both TβRIII-mediated inhibition of TGF-β signaling and TβRIII-mediated inhibition of invasion occur through the interaction of the cytoplasmic domain of TβRIII with the scaffolding protein GAIP-interacting protein C-terminus (GIPC). Taken together, these studies support a functional role for the TβRIII cytoplasmic domain interacting with GIPC to suppress breast cancer progression.

Journal Article.  5670 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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