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Type III TGF-? receptor enhances colon cancer cell migration and anchorage-independent growth.

ABSTRACT: The type III TGF-? receptor (T?RIII or betagylcan) is a TGF-? superfamily coreceptor with emerging roles in regulating TGF-? superfamily signaling and cancer progression. Alterations in TGF-? superfamily signaling are common in colon cancer; however, the role of T?RIII has not been examined. Although T?RIII expression is frequently lost at the message and protein level in human cancers and suppresses cancer progression in these contexts, here we demonstrate that, in colon cancer, T?RIII messenger RNA expression is not significantly altered and T?RIII expression is more frequently increased at the protein level, suggesting a distinct role for T?RIII in colon cancer. Increasing T?RIII expression in colon cancer model systems enhanced ligand-mediated phosphorylation of p38 and the Smad proteins, while switching TGF-? and BMP-2 from inhibitors to stimulators of colon cancer cell proliferation, inhibiting ligand-induced p21 and p27 expression. In addition, increasing T?RIII expression increased ligand-stimulated anchorage-independent growth, a resistance to ligand- and chemotherapy-induced apoptosis, cell migration and modestly increased tumorigenicity in vivo. In a reciprocal manner, silencing endogenous T?RIII expression decreased colon cancer cell migration. These data support a model whereby T?RIII mediates TGF-? superfamily ligand-induced colon cancer progression and support a context-dependent role for T?RIII in regulating cancer progression.


PROVIDER: S-EPMC3156666 | BioStudies | 2011-01-01

REPOSITORIES: biostudies

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