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

Background Calcyclin 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. Methods The 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. Results We 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. Conclusion Thus, we demonstrated that S100A6 is required for the Ca2+-dependent nuclear translocation of CacyBP/SIP in colon cancer SW480 cells.

[1]  D. Fan,et al.  CacyBP/SIP promotes the proliferation of colon cancer cells , 2017, PloS one.

[2]  Yuanyuan Lu,et al.  CacyBP/SIP nuclear translocation regulates p27Kip1 stability in gastric cancer cells. , 2016, World journal of gastroenterology.

[3]  Haifeng Jin,et al.  Role of the CacyBP/SIP protein in gastric cancer. , 2015, Oncology letters.

[4]  H. Zhai,et al.  CacyBP/SIP nuclear translocation induced by gastrin promotes gastric cancer cell proliferation. , 2014, World journal of gastroenterology.

[5]  W. Hwang,et al.  Effects of repetitive ionomycin treatment on in vitro development of bovine somatic cell nuclear transfer embryos. , 2012, The Journal of reproduction and development.

[6]  C. Heizmann,et al.  The importance of Ca2+/Zn2+ signaling S100 proteins and RAGE in translational medicine. , 2011, Frontiers in bioscience.

[7]  A. Filipek,et al.  S100A6 binding protein and Siah-1 interacting protein (CacyBP/SIP): spotlight on properties and cellular function , 2011, Amino Acids.

[8]  A. Filipek,et al.  S100A6 - new facts and features. , 2009, Biochemical and biophysical research communications.

[9]  R. Caprioli,et al.  Structure of the S100A6 complex with a fragment from the C-terminal domain of Siah-1 interacting protein: a novel mode for S100 protein target recognition. , 2008, Biochemistry.

[10]  Haifeng Jin,et al.  Expression of Calcyclin-binding Protein/Siah-1 Interacting Protein in Normal and Malignant Human Tissues: An Immunohistochemical Survey , 2008, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[11]  D. Fan,et al.  Establishment and characterization of calcyclin binding protein (CacyBP) monoclonal antibody. , 2006, Hybridoma.

[12]  Jing Wu,et al.  Translocation and phosphorylation of calcyclin binding protein during retinoic acid-induced neuronal differentiation of neuroblastoma SH-SY5Y cells. , 2003, Journal of biochemistry and molecular biology.

[13]  J. Kuźnicki,et al.  CacyBP/SIP, a Calcyclin and Siah-1-interacting Protein, Binds EF-hand Proteins of the S100 Family* , 2002, The Journal of Biological Chemistry.

[14]  J. Kuźnicki,et al.  Ca2+-dependent Translocation of the Calcyclin-binding Protein in Neurons and Neuroblastoma NB-2a Cells* , 2002, The Journal of Biological Chemistry.

[15]  J. Kuźnicki,et al.  Ca 2-dependent Translocation of the Calcyclin-binding Protein in Neurons and Neuroblastoma NB2 a Cells * , 2002 .

[16]  J C Reed,et al.  Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses. , 2001, Molecular cell.

[17]  J. Kuźnicki,et al.  Molecular Cloning and Expression of a Mouse Brain cDNA Encoding a Novel Protein Target of Calcyclin , 1998, Journal of neurochemistry.