The effect of S100A6 on nuclear translocation of CacyBP/SIP in colon cancer cells

Abstract

BackgroundCalcyclin Binding Protein/(Siah-1 interacting protein) (CacyBP/SIP) acts as an oncogene in colorectal cancer. The nuclear accumulation of CacyBP/SIP has been linked to the proliferation of cancer cells. It has been reported that intracellular Ca2+ induces the nuclear translocation of CacyBP/SIP. However, the molecular mechanism of CacyBP/SIP nuclear translocation has yet to be elucidated. The purpose of this study was to test whether the Ca2+-dependent binding partner S100 protein is involved in CacyBP/SIP nuclear translocation in colon cancer SW480 cells.MethodsThe subcellular localization of endogenous CacyBP/SIP was observed following the stimulation of ionomycin or BAPTA/AM by immunofluorescence staining in SW480 cells. S100A6 small interfering RNAs (siRNA) were transfected into SW480 cells. Immunoprecipitation assays detected whether S100 protein is relevant to the nuclear translocation of CacyBP/SIP in response to changes in [Ca2+]i.ResultsWe observed that endogenous CacyBP/SIP is translocated from the cytosol to the nucleus following the elevation of [Ca2+]i by ionomycin in SW480 cells. Co-immunoprecipitation experiments showed that the interaction between S100A6 and CacyBP/SIP was increased simultaneously with elevated Ca2+. Knockdown of S100A6 abolished the Ca2+ effect on the subcellular translocation of CacyBP/SIP.ConclusionThus, we demonstrated that S100A6 is required for the Ca2+-dependent nuclear translocation of CacyBP/SIP in colon cancer SW480 cells.

Bioinformatic analysis of Cacybp‐associated proteins using human glioma databases

“…As Cacybp is an E3 ubiquitin ligase, we hypothesized that the 46 downregulated genes may include ubiquitinated substrates of Cacybp. The current focus of research is mainly Cacybp nuclear transfer (11,13,21,22) and phosphorylation activities (23)(24)(25)(26), which is consistent with our results. Using Cytoscape software we identified biological processes and molecular functions that may be affected by Cacybp.…”

“…We identified genes closely related to Cacybp expression through bioinformatics software analysis, but determining which of these differential genes are targets of Cacybp and which are ubiquitinated substrates requires further study. The current focus of research is mainly Cacybp nuclear transfer (11,13,21,22) and phosphorylation activities (23)(24)(25)(26), which is consistent with our results. In addition, we also found that Cacybp is involved in cell secretion and examined Cacybp expression in glioma patients and its relationship with prognosis.…”

“…Previous studies found that Cacybp plays an irreplaceable role in the development of tumors such as glioma (12), colon cancer (16), gastric cancer (13,17), and others (18). However, whether Cacybp influences genes that cause tumor development has been widely debated (11,19,20). We identified genes closely related to Cacybp expression through bioinformatics software analysis, but determining which of these differential genes are targets of Cacybp and which are ubiquitinated substrates requires further study.…”

“…Studies have reported that Cacybp is involved in colon cancer (11), glioma (12), gastric cancer (13), and pancreatic cancer (14). Studies have reported that Cacybp is involved in colon cancer (11), glioma (12), gastric cancer (13), and pancreatic cancer (14).…”

“…Studies have reported that Cacybp is involved in colon cancer (11), glioma (12), gastric cancer (13), and pancreatic cancer (14). Although there have been a large number of studies on the mechanisms of Cacybp in the early stage of tumorigenesis, these mainly focus on one or a few specific aspects (11)(12)(13)(14). To systematically study the mechanism of action of Cacybp in tumors, we selected human glioma data for analysis by bioinformatics.…”