Calcyclin-Binding Protein Inhibits Proliferation, Tumorigenicity, and Invasion of Gastric Cancer

Abstract

Calcyclin-binding protein/Siah-1 -interacting protein (CacyBP/SIP), a target protein of the S100 family, which includes S100A6, S100A1, S100A12, S100B, and S100P, has been identified as a component of a novel ubiquitinylation complex leading to B-catenin degradation. However, the function of CacyBP/SIP in gastric cancer has not been elucidated. In the present study, we prepared CacyBP/SIP overexpressing and knockdown cell lines of gastric cancer. Forced CacyBP/SIP expression inhibited the proliferation of gastric cancer cells, suppressed tumorigenicity in vitro, and prolonged the survival time of tumor-bearing nude mice. In addition, increased CacyBP/SIP repressed the invasive potential of gastric cancer cells. Conversely, the down-regulation of CacyBP/SIP by RNA interference showed the opposite effects. Further studies showed that depressed CacyBP/SIP increased the expression of total and nuclear B-catenin at the protein level and elevated the transcriptional activity of Tcf/LEF. Taken together, our results suggest that CacyBP/SIP may be a potential inhibitor of cell growth and invasion in the gastric cancer cell, at least in part through the effect on B-catenin protein expression and transcriptional activation of Tcf/LEF.

Direct Ubiquitination of β-Catenin by Siah-1 and Regulation by the Exchange Factor TBL1

“…S2B). It has been reported that overexpression of SIP mutants that cannot interact with Siah-1 prevent the efficient degradation of ␤-catenin in HEK293T cells, and the level of SIP is essential for ␤-catenin degradation in gastric and renal cancer cells (35)(36)(37). However, overexpression of only Siah-1 is sufficient for ␤-catenin degradation in cells, and the in vitro ubiquitination of ␤-catenin is not affected by the addition of SIP (Fig.…”

“…Liu and co-workers (7,35) showed that APC is required to observe Siah-1-mediated degradation of ␤-catenin in cells and that APC directly interacts with Siah-1 and with ␤-catenin. Our data indicate that Siah-1 binding to ␤-catenin is very dynamic and weak (Fig.…”

Siah1/SIP regulates p27kip1stability and cell migration under metabolic stress

“…Furthermore, a recent study has shown that downregulation of SIP by RNA interference increases tumorigenicity and invasiveness of gastric cancer cells. 48 Recently, Schneider and coworkers reported that SIP interacts with tubulin to increase tubulin assemblies in neuroblastoma cells, suggesting that SIP/CacyBP regulates microtubule dynamics and plays a role in cell migration. 49 Thus, we hypothesize that via their degradation of cytosolic p27, Siah/SIP plays important roles in cell motility.…”

Integrated Network Analysis of Genetic and Epigenetic Factors in Glioblastoma Multiform

“…It was also reported that CACYBP participates in p53-induced beta-catenin degradation and can suppress proliferation and tumorigenesis of renal cancer cells (Sun, et al, 2007). CACYBP was under expressed in gastric cancer (Ning, et al, 2007) and renal cancer (Sun, et al, 2007). Fig.…”