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

<div><p>Background</p><p>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.</p><p>Methods</p><p>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>i</i>.</p><p>Results</p><p>We observed that endogenous CacyBP/SIP is translocated from the cytosol to the nucleus following the elevation of [Ca²⁺]<i>i</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.</p><p>Conclusion</p><p>Thus, we demonstrated that S100A6 is required for the Ca²⁺-dependent nuclear translocation of CacyBP/SIP in colon cancer SW480 cells.</p>