Calcyclin-binding protein inhibits proliferation, tumorigenicity, and invasion of gastric cancer.
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 beta-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 beta-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 beta-catenin protein expression and transcriptional activation of Tcf/LEF.
Ning
Xiaoxuan
X
Department of Geriatrics, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
Sun
Shiren
S
Hong
Liu
L
Liang
Jie
J
Liu
Lili
L
Han
Shuang
S
Liu
Zhiguo
Z
Shi
Yongquan
Y
Li
Yuan
Y
Gong
Weiqin
W
Zhang
Shanhong
S
Chen
Yu
Y
Guo
Xueyan
X
Cheng
Yi
Y
Wu
Kaichun
K
Fan
Daiming
D
D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015533:Transcriptional Activation / Q000502:physiology; D014162:Transfection; D015854:Up-Regulation / Q000502:physiology; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
C491778:CACYBP protein, human; D002135:Calcium-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D034741:RNA, Small Interfering; D051176:beta Catenin