βII-Spectrin (SPTBN1) suppresses progression of hepatocellular carcinoma and Wnt signaling by regulation of Wnt inhibitor kallistatin.

ABSTRACT:

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βII-Spectrin (SPTBN1) is an adapter protein for Smad3/Smad4 complex formation during transforming growth factor beta (TGF-β) signal transduction. Forty percent of SPTBN1(+/-) mice spontaneously develop hepatocellular carcinoma (HCC), and most cases of human HCC have significant reductions in SPTBN1 expression. In this study, we investigated the possible mechanisms by which loss of SPTBN1 may contribute to tumorigenesis. Livers of SPTBN1(+/-) mice, compared to wild-type mouse livers, display a significant increase in epithelial cell adhesion molecule-positive (EpCAM(+)) cells and overall EpCAM expression. Inhibition of SPTBN1 in human HCC cell lines increased the expression of stem cell markers EpCAM, Claudin7, and Oct4, as well as decreased E-cadherin expression and incr

SUBMITTER: Zhi X 

PROVIDER: S-EPMC4327990 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature